Name: 29886-64-4|4-(Thiophen-3-yl)benzoic acid|95%
Brand: Ambeed
SKU: A317840
Price: 37.0 USD
Availability: InStock
Rating: 94 (22 reviews)

1
[ 6165-69-1 ]
[ 1711-02-0 ]
[ 29886-64-4 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-iodobenzoic acid chloride; DR⁹_HMPA-CH₂OH With dmap; TEA In pyridine at 20℃; for 36h; Stage #2: Thien-3-ylboronic acid With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In water; N,N-dimethyl-formamide at 110℃; Stage #3: With trifluoroacetic acid In dichloromethane at 20℃; for 1h;

Reference： [1]Zhang, Jidong; Aszodi, Jozsef; Chartier, Céline; L'Hermite, Nathalie; Weston, John [Tetrahedron Letters, 2001, vol. 42, # 38, p. 6683 - 6686]

2
[ 304690-94-6 ]
[ 29886-64-4 ]
<i>N</i>-(1-methyl-1,2,3,4-tetrahydro-quinolin-7-yl)-4-thiophen-3-yl-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;

Reference： [1]Westaway, Susan M.; Chung, Ying-Kit; Davis, John B.; Holland, Vicky; Jerman, Jeffrey C.; Medhurst, Stephen J.; Rami, Harshad K.; Stemp, Geoffrey; Stevens, Alexander J.; Thompson, Mervyn; Winborn, Kim Y.; Wright, James [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4533 - 4536]

3
[ 872-31-1 ]
[ 14047-29-1 ]
[ 29886-64-4 ]

Yield	Reaction Conditions	Operation in experiment
94%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In ethanol; water at 90℃; Inert atmosphere;

Reference： [1]Location in patent: experimental part Holzer, Marcel; Ziegler, Sigrid; Neugebauer, Alexander; Kronenberger, Bernd; Klein, Christian D.; Hartmann, Rolf W. [Archiv der Pharmazie, 2008, vol. 341, # 8, p. 478 - 484]

4
[ 29886-64-4 ]
[ 181132-79-6 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride at 20℃; for 2h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 4h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Holzer, Marcel; Ziegler, Sigrid; Neugebauer, Alexander; Kronenberger, Bernd; Klein, Christian D.; Hartmann, Rolf W. [Archiv der Pharmazie, 2008, vol. 341, # 8, p. 478 - 484]
[2]Kalsi, Deepti; Barsu, Nagaraju; Sundararaju, Basker [Chemistry - A European Journal, 2018, vol. 24, # 10, p. 2360 - 2364]

5
[ 29886-64-4 ]
[ 1138217-76-1 ]
[ 1269797-53-6 ]

Yield	Reaction Conditions	Operation in experiment
62%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;

Reference： [1]Location in patent: experimental part Tu, Zhude; Li, Shihong; Cui, Jinquan; Xu, Jinbin; Taylor, Michelle; Ho, David; Luedtke, Robert R.; MacH, Robert H. [Journal of Medicinal Chemistry, 2011, vol. 54, # 6, p. 1555 - 1564]

6
[ 29886-64-4 ]
[ 1269797-24-1 ]
[ 1269797-65-0 ]

Yield	Reaction Conditions	Operation in experiment
62%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;

Reference： [1]Location in patent: experimental part Tu, Zhude; Li, Shihong; Cui, Jinquan; Xu, Jinbin; Taylor, Michelle; Ho, David; Luedtke, Robert R.; MacH, Robert H. [Journal of Medicinal Chemistry, 2011, vol. 54, # 6, p. 1555 - 1564]

7
[ 29886-64-4 ]
[ 1435684-52-8 ]
[ 1435684-92-6 ]

Yield	Reaction Conditions	Operation in experiment
86%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 15h;	7.12. General procedure for preparing the substitutedbenzamide analogues N-(4-(4-(2-methoxyphenyl)-1,4-diazepan-1-yl)butyl)-4-(thiophen-3-yl)benzamide (11a) General procedure: A mixture of compound 10 (135 mg, 0.49 mmol) and 4-(thiophen-3-yl)benzoic acid (99.4 mg, 0.49 mmol) in dichloromethane (10 mL) was stirred at 0 °C (ice-water bath). Dicyclohexylcarbodiimide(DCC) (121 mg, 0.59 mmol) and hydroxybenzotriazole(HOBt) (80 mg, 0.59 mmol) were added to the above solution.The ice bath was removed, and the reaction mixture was stirred at ambient temperature for 15 h. Dichloromethane (20 mL) was added into the reaction mixture, and the solution was washed with saturated aqueous NaHCO3 solution (3*10 mL). The organic layer was dried over Na2SO4, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography using dichloromethane-methanol (20:1) as the mobile phase to give 11a as a white solid (194 mg, 86%). TLC Rf 0.20 (dichloromethane-methanol 20:1); mp 125.5-126.6 °C. 1H NMR(300 MHz, CDCl3) δ 7.75 (d, J = 8.7 Hz, 2H), 7.54 (d, J = 8.7 Hz, 2H),7.43 (s, 1H), 7.33 (s, 2H), 7.19 (s, 1H), 6.81-6.94 (m, 4H), 3.85 (s,3H), 3.44 (q, J = 5.1 Hz, 2H), 3.25-3.20 (m, 4H), 2.83-2.76 (m,4H), 2.57 (t, J = 5.2 Hz, 2H), 1.93 (t, J = 4.2 Hz, 2H), 1.61-1.69 (m,4H). 13C NMR (CDCl3, 300 MHz): 167.4, 151.4, 142.1, 141.2,138.8, 133.4, 127.5, 126.6, 126.3, 126.1, 121.3, 121.0, 120.7,117.9, 111.6, 57.1, 56.1, 55.3, 54.3, 52.5, 51.8, 39.4, 27.7, 27.3,25.5. HRMS (ESI) Calcd for C27H33N3O2S (M+H)+: 464.2372. Found:464.2379. Anal. (C27H33N3O2S 1.5H2C2O4) C, H, N.

Reference： [1]Li, Aixiao; Mishra, Yogesh; Malik, Maninder; Wang, Qi; Li, Shihong; Taylor, Michelle; Reichert, David E.; Luedtke, Robert R.; MacH, Robert H. [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 11, p. 2988 - 2998]

8
[ 29886-64-4 ]
[ 160278-20-6 ]

Yield	Reaction Conditions	Operation in experiment
65%	With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 4h; Inert atmosphere;	45.1 Preparation of [4-(3-thienyl)-phenyl]-methanol Under nitrogen atmosphere, at 0 °C, to a stirring mixture of L1AIH4 (2.0 M THF solution, 3.92 mL, 7.84 mmol) in dry THF (6.0 mL), commercially available 4-(3-thienyl)- benzoic acid (0.4 g, 1.96 mmol) in dry THF (30 mL) was added dropwise. The mixture was left to react at rt for 4 h, then at 0 °C H20 (0.30 mL), 3.0 M KOH solution (0.30 mL) and H20 (1.0 mL) were very slowly added. The mixture was stirred for 1 h at 0 °C, filtered to remove the solid residue, and the organic phase dried over Na2S04. The organic solution was again filtered and concentrated to dryness, affording the title compound (0.222 g, 65%), which was used in the next step without any further purification. 1H NMR (DMSO-d6): δ 4.51 (d, J = 5.75 Hz, 2H), 5.17 (t, J = 5.75 Hz, 1H), 7.35 (d, J = 8.1 Hz, 2H), 7.52 - 7.57 (m, 1H), 7.63 (dd, J = 2.9, 5.0 Hz, 1H), 7.67 (d, J = 8.1 Hz, 2H), 7.81 - 7.86 (m, 1H).
65%	With lithium aluminium tetrahydride In diethyl ether at 0 - 20℃; for 4h; Inert atmosphere;
65%	With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 4h; Inert atmosphere;	45.1 Step 1. Step 1. Preparation of [4-(3-thienyl)-phenyl]-methanol Under nitrogen atmosphere, at 0° C., to a stirring mixture of LiAlH4 (2.0 M THF solution, 3.92 mL, 7.84 mmol) in dry THF (6.0 mL), commercially available 4-(3-thienyl)-benzoic acid (0.4 g, 1.96 mmol) in dry THF (30 mL) was added dropwise. The mixture was left to react at rt for 4 h, then at 0° C. H2O (0.30 mL), 3.0 M KOH solution (0.30 mL) and H2O (1.0 mL) were very slowly added. The mixture was stirred for 1 h at 0° C., filtered to remove the solid residue, and the organic phase dried over Na2SO4. The organic solution was again filtered and concentrated to dryness, affording the title compound (0.222 g, 65%), which was used in the next step without any further purification. 1H NMR (DMSO-d6): δ 4.51 (d, J=5.75 Hz, 2H), 5.17 (t, J=5.75 Hz, 1H), 7.35 (d, J=8.1 Hz, 2H), 7.52-7.57 (m, 1H), 7.63 (dd, J=2.9, 5.0 Hz, 1H), 7.67 (d, J=8.1 Hz, 2H), 7.81-7.86 (m, 1H).

Reference： [1]Current Patent Assignee: UNIVERSITY OF PARMA; UNIVERSITY OF URBINO; UNIVERSITY OF CALIFORNIA; ISTITUTO ITALIANO DI TECNOLOGIA - WO2013/78430, 2013, A1 Location in patent: Paragraph 0357
[2]Ponzano, Stefano; Berteotti, Anna; Petracca, Rita; Vitale, Romina; Mengatto, Luisa; Bandiera, Tiziano; Cavalli, Andrea; Piomelli, Daniele; Bertozzi, Fabio; Bottegoni, Giovanni [Journal of Medicinal Chemistry, 2014, vol. 57, # 23, p. 10101 - 10111]
[3]Current Patent Assignee: UNIVERSITY OF PARMA; UNIVERSITY OF URBINO; UNIVERSITY OF CALIFORNIA; ISTITUTO ITALIANO DI TECNOLOGIA - US9353075, 2016, B2 Location in patent: Page/Page column 123; 124

9
[ 29886-64-4 ]
[ 1439368-16-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 0 - 20 °C / Inert atmosphere 2.1: dmap / dichloromethane / 15 h / 20 °C / Inert atmosphere 2.2: 15 h / 20 °C
	Multi-step reaction with 2 steps 1.1: lithium aluminium tetrahydride / diethyl ether / 4 h / 0 - 20 °C / Inert atmosphere 2.1: dmap / dichloromethane / 15 h / 20 °C / Inert atmosphere 2.2: 15 h / 20 °C
	Multi-step reaction with 2 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 0 - 20 °C / Inert atmosphere 2.1: dmap / dichloromethane / 15 h / 20 °C / Inert atmosphere 2.2: 15 h / 20 °C

Reference： [1]Current Patent Assignee: UNIVERSITY OF PARMA; UNIVERSITY OF URBINO; UNIVERSITY OF CALIFORNIA; ISTITUTO ITALIANO DI TECNOLOGIA - WO2013/78430, 2013, A1
[2]Ponzano, Stefano; Berteotti, Anna; Petracca, Rita; Vitale, Romina; Mengatto, Luisa; Bandiera, Tiziano; Cavalli, Andrea; Piomelli, Daniele; Bertozzi, Fabio; Bottegoni, Giovanni [Journal of Medicinal Chemistry, 2014, vol. 57, # 23, p. 10101 - 10111]
[3]Current Patent Assignee: UNIVERSITY OF PARMA; UNIVERSITY OF URBINO; UNIVERSITY OF CALIFORNIA; ISTITUTO ITALIANO DI TECNOLOGIA - US9353075, 2016, B2

10
[ 29886-64-4 ]
[ 1439366-96-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 0 - 20 °C / Inert atmosphere 2.1: dmap / dichloromethane / 15 h / 20 °C / Inert atmosphere 2.2: 15 h / 20 °C 3.1: triethylamine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1.1: lithium aluminium tetrahydride / diethyl ether / 4 h / 0 - 20 °C / Inert atmosphere 2.1: dmap / dichloromethane / 15 h / 20 °C / Inert atmosphere 2.2: 15 h / 20 °C 3.1: triethylamine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 0 - 20 °C / Inert atmosphere 2.1: dmap / dichloromethane / 15 h / 20 °C / Inert atmosphere 2.2: 15 h / 20 °C 3.1: triethylamine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: UNIVERSITY OF PARMA; UNIVERSITY OF URBINO; UNIVERSITY OF CALIFORNIA; ISTITUTO ITALIANO DI TECNOLOGIA - WO2013/78430, 2013, A1
[2]Ponzano, Stefano; Berteotti, Anna; Petracca, Rita; Vitale, Romina; Mengatto, Luisa; Bandiera, Tiziano; Cavalli, Andrea; Piomelli, Daniele; Bertozzi, Fabio; Bottegoni, Giovanni [Journal of Medicinal Chemistry, 2014, vol. 57, # 23, p. 10101 - 10111]
[3]Current Patent Assignee: UNIVERSITY OF PARMA; UNIVERSITY OF URBINO; UNIVERSITY OF CALIFORNIA; ISTITUTO ITALIANO DI TECNOLOGIA - US9353075, 2016, B2

11
[ 29886-64-4 ]
[ 524-38-9 ]
1,3-dioxoisoindolin-2-yl 4-(thiophen-3-yl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With dicyclohexyl-carbodiimide In ethyl acetate at 20℃; for 3h; Inert atmosphere;

Reference： [1]Candish, Lisa; Teders, Michael; Glorius, Frank [Journal of the American Chemical Society, 2017, vol. 139, # 22, p. 7440 - 7443]

12
[ 29886-64-4 ]
C₁₉H₃₃N₃ [ No CAS ]
C₃₀H₃₉N₃OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In tetrahydrofuran at 20℃; Inert atmosphere;

Reference： [1]Dang, Zhao; Xie, Hua; Zhu, Lei; Zhang, Qingye; Li, Zhijun; Huang, Li; Chen, Chin-Ho [ACS Medicinal Chemistry Letters, 2017, vol. 8, # 11, p. 1199 - 1203]

13
[ 29886-64-4 ]
[ 73183-34-3 ]
[ 1359844-12-4 ]

Yield	Reaction Conditions	Operation in experiment
94%	With palladium diacetate; 2,2-dimethylpropanoic anhydride; triethylamine; 1,4-di(diphenylphosphino)-butane In 1,4-dioxane at 160℃; for 15h;

Reference： [1]Liu, Chengwei; Ji, Chong-Lei; Hong, Xin; Szostak, Michal [Angewandte Chemie - International Edition, 2018, vol. 57, # 51, p. 16721 - 16726][Angew. Chem., 2018, vol. 130, p. 16963 - 16968,6]

14
[ 29886-64-4 ]
4-(9-(2-methoxyphenyl)-3,9-diazaspiro[5.5]undecan-3-yl)butan-1-amine [ No CAS ]
N-(4-(9-(2-methoxyphenyl)-3,9-diazaspiro[5.5]undecan-3-yl)-butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 2h;
31%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 2h;	N-( 4-(9-(2-Methoxyphenyl)-3, 9-diazaspirof 5.5 ]undecan-3-yl)butyl)-4-( thiophen-3- yljbenzamide (35). [000275] H (1.0 mmol), 4-(thiophen-3-yl)benzoic acid (1.1 mmol), 1-hydroxybenzotriazole (HOBt) hydrate (1.0 mmol), l-ethyl-3-(3'-dimethylaminopropyl)carbodiimide (EDC) HCl (1.0 mmol) were stirred in 15 mL of CH2CI2 at room temperature for 2 h. The reaction mixture was then washed with a saturated NaHCCb (aq) solution (10 mL). The reaction mixture was extracted with CH2CI2 (3 x 20 mL), and the organic layers were combined, dried, and concentrated to afford a crude white sold. Residue was purified by flash chromatography on silica gel eluding with MeOH/CH2Cl2 (1 : 10) to afford 35 as a white solid. (Yield 31%) NMR (500 MHz, (CD3)2SO) δ 8.66 (m, 1H), 8.00 (bs, 1H), 7.95 (d, J= 7.7 Hz, 2H), 7.82 (d, J= 8.2 Hz, 2H), 7.67- 7.65 (m, 1H), 7.63-7.62 (m, 1H), 6.91-6.88 (m, 3H), 6.85-6.83 (m, 1H), 3.75 (s, 3H), 3.31 (quint, J= 5.9 Hz, 2H), 2.96-2.87 (m, 9H), 1.69 (bs, 6H), 1.57-1.56 (m, 6H); 13C NMR (125 MHz, (CD3)2SO) 5 165.7, 152.0, 141.8, 140.5, 137.5, 132.8, 127.9, 127.3, 126.2, 125.7, 122.3, 122.2, 120.7, 118.1, 111.7, 55.2, 47.5, 45.8, 38.5, 32.6, 28.4, 26.5, 21.5; LC-MS (ESI) m/z: 518.22

Reference： [1]Reilly, Sean W.; Riad, Aladdin A.; Hsieh, Chia-Ju; Sahlholm, Kristoffer; Jacome, Daniel A.; Griffin, Suzy; Taylor, Michelle; Weng, Chi-Chang; Xu, Kuiying; Kirschner, Nathan; Luedtke, Robert R.; Parry, Christopher; Malhotra, Shipra; Karanicolas, John; Mach, Robert H. [Journal of Medicinal Chemistry, 2019, vol. 62, # 10, p. 5132 - 5147]
[2]Current Patent Assignee: UNIVERSITY OF PENNSYLVANIA - WO2019/84075, 2019, A1 Location in patent: Paragraph 000161; 000274-000275

15
[ 29886-64-4 ]
[ 2404-87-7 ]

Yield	Reaction Conditions	Operation in experiment
79%	With triethylsilane; palladium diacetate; 2,2-dimethylpropanoic anhydride; 1,4-di(diphenylphosphino)-butane In toluene at 160℃; for 15h; chemoselective reaction;

Reference： [1]Liu, Chengwei; Qin, Zhi-Xin; Ji, Chong-Lei; Hong, Xin; Szostak, Michal [Chemical Science, 2019, vol. 10, # 22, p. 5736 - 5742]

16
[ 64-18-6 ]
[ 29886-64-4 ]
[ 21237-61-6 ]
N-(4-(4-(2-chlorophenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide formate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: formic acid; 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 4-amino-1-(4-(2-chlorophenyl)piperazin-1-yl)butane In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

17
[ 64-18-6 ]
[ 29886-64-4 ]
[ 21098-01-1 ]
N-(4-(4-(2-methylphenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide formate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: formic acid; 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 4-[4-(2-methyl-phenyl)piperazine]-1-butylamine In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

18
[ 64-18-6 ]
[ 29886-64-4 ]
C₁₅H₂₂N₄ [ No CAS ]
N-(4-(4-(2-cyanophenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide formate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: formic acid; 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: C₁₅H₂₂N₄ In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

19
[ 64-18-6 ]
[ 29886-64-4 ]
[ 1003861-86-6 ]
N-(4-(4-(3-cyanophenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide formate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: formic acid; 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 4-[4-(3-cyano-phenyl)-piperazin-1-yl]-butylamine In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

20
[ 64-18-6 ]
[ 29886-64-4 ]
4-amino-1-(4-(4-cyanophenyl)piperazin-1-yl)butane [ No CAS ]
N-(4-(4-(4-cyanophenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide formate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: formic acid; 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 4-amino-1-(4-(4-cyanophenyl)piperazin-1-yl)butane In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

21
[ 64-18-6 ]
[ 29886-64-4 ]
4-[4-[2-(trifluoromethyl)phenyl]piperazin-1-yl]butan-1-amine [ No CAS ]
N-(4-(4-(2-trifluoromethylphenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide formate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: formic acid; 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 4-[4-[2-(trifluoromethyl)phenyl]piperazin-1-yl]butan-1-amine In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

22
[ 64-18-6 ]
[ 29886-64-4 ]
[ 82278-36-2 ]
N-(4-(4-(3-trifluoromethylphenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide formate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: formic acid; 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 1-(4-aminobutyl)-4-[3-(trifluoromethyl)phenyl]piperazine In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

23
[ 64-18-6 ]
[ 29886-64-4 ]
C₁₅H₂₂F₃N₃ [ No CAS ]
N-(4-(4-(4-trifluoromethylphenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide formate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: formic acid; 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: C₁₅H₂₂F₃N₃ In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

24
[ 29886-64-4 ]
[ 40255-41-2 ]
N-(4-(4-phenylpiperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 4-(4-phenylpiperazin-1-yl)butan-1-amine In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

25
[ 29886-64-4 ]
4-(4-(3-chlorophenyl)-piperazin-1-yl)-butan-1-amine [ No CAS ]
N-(4-(4-(3-chlorophenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 4-(4-(3-chlorophenyl)-piperazin-1-yl)-butan-1-amine In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

26
[ 29886-64-4 ]
[ 92328-97-7 ]
N-(4-(4-(4-chlorophenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 4-(4-chlorophenyl)-1-piperazinebutanamine In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

27
[ 29886-64-4 ]
[ 189061-44-7 ]
N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butylamine In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

28
[ 29886-64-4 ]
C₁₄H₂₁Cl₂N₃ [ No CAS ]
N-(4-(4-(2,4-dichlorophenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: C₁₄H₂₁Cl₂N₃ In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

29
[ 29886-64-4 ]
C₁₄H₂₁Cl₂N₃ [ No CAS ]
N-(4-(4-(3,5-dichlorophenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: C₁₄H₂₁Cl₂N₃ In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

30
[ 29886-64-4 ]
[ 21103-33-3 ]
N-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 4-[4-(2-methoxyphenyl)piperazin-1-yl]butylamine In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

31
[ 29886-64-4 ]
[ 898533-23-8 ]
N-(4-(4-(3-methoxyphenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 4-(4-(3-methoxyphenyl)piperazin-1-yl)butan-1-amine In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

32
[ 29886-64-4 ]
[ 1016675-06-1 ]
N-(4-(4-(4-methoxyphenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 4-(4-(4-methoxyphenyl)piperazin-1-yl)butan-1-amine In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

33
[ 29886-64-4 ]
[ 927187-09-5 ]
N-(4-(4-(2-hydroxyphenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 2-[4-(4-aminobutyl)-1-piperazinyl]phenol In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

34
[ 29886-64-4 ]
[ 1137920-94-5 ]
N-(4-(4-(3-hydroxyphenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 3-[4-(4-aminobutyl)-1-piperazinyl]phenol In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

35
[ 29886-64-4 ]
[ 1608490-88-5 ]
N-(4-(4-(4-hydroxyphenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: C₁₄H₂₃N₃O In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

36
[ 29886-64-4 ]
1-(4-aminobutyl)-4-(3-methylphenyl)piperazine [ No CAS ]
N-(4-(4-(3-methylphenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 1-(4-aminobutyl)-4-(3-methylphenyl)piperazine In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

37
[ 29886-64-4 ]
1-(4-aminobutyl)-4-(4-methylphenyl)piperazine [ No CAS ]
N-(4-(4-(4-methylphenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 1-(4-aminobutyl)-4-(4-methylphenyl)piperazine In ethanol at 23℃; for 16h;	Step 4: General procedure: A solution of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM, 0.44 g, 1.56 mmol, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (10) (0.32 g, 1.56 mmol, 1.1 eq) in ethanol (10 ml) was stirred at 23 oC. After 1 hour, the 4-(4-arylpiperazin-1-yl)butan-1-amine prepared in step 3 (15a-v) (1.42 mmol) was added, and the reaction was stirred at 23 oC for an additional 16 hours. The reaction was then filtered to remove precipitates and stripped of solvents. The residual material was purified by normal phase chromatography (10% methanol/0.1% ammonium hydroxide in dichloromethane) or reverse phase chromatography (5% acetonitrile/0.1% formic acid in water) as necessary to provide the desired product.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

38
[ 29886-64-4 ]
[ 13325-10-5 ]
N-(4-hydroxybutyl)-4-thiophen-3ylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(thiophen-3-yl)benzoic acid With 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride In ethanol at 23℃; for 1h; Stage #2: 4-Aminobutanol In ethanol at 23℃; for 16h;	Step 1: 4-(4,6-dimethoxy-1,2,5-triazin-2yl)-4-methylmorpholinium chloride (DMT-MM, 120 g, 43.2 mmole, 1.1 eq) and 4-(thiophen-3-yl)benzoic acid (3) (8.0g, 39.2mmol) were dissolved in ethanol (100 ml) and the reaction was stirred at 23 oC. After 1 hour, 4-aminobutan-1-ol (4.0 ml, 42.2 mmol, 1.1 eq) was added and the reaction was stirred at 23 oC for an additional 16 hours. The mixture was filtered to remove insoluble materials, stripped of solvent and the residue was purified by normal phase chromatography to provide N-(4-hydroxybutyl)-4-thiophen-3yl)benzamide. H NMR (400 mHz, MeOD-d4) δ 7.87 (d. J = 856 Hz, 2H), 7.78-7.76 (m,3H), 7.53 (d, J = 2.16 Hz, 2H), 3.63 (d, J = 6.4HZ, 2H), 3.32 (pent, 6H); MS (LC/MS, M+H); 276.10.

Reference： [1]Chen, Peng-Jen; Taylor, Michelle; Griffin, Suzy A.; Amani, Armaghan; Hayatshahi, Hamed; Korzekwa, Kenneth; Ye, Min; Mach, Robert H.; Liu, Jin; Luedtke, Robert R.; Gordon, John C.; Blass, Benjamin E. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 18, p. 2690 - 2694]

39
[ 29886-64-4 ]
[ 762-04-9 ]
diethyl (4-(thiophen-3-yl)phenyl)phosphonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With palladium diacetate; 2,2-dimethylpropanoic anhydride; triethylamine; 1,4-di(diphenylphosphino)-butane In 1,4-dioxane at 160℃; for 15h; Inert atmosphere; Schlenk technique;

Reference： [1]Liu, Chengwei; Ji, Chong-Lei; Zhou, Tongliang; Hong, Xin; Szostak, Michal [Organic Letters, 2019, vol. 21, # 22, p. 9256 - 9261]

40
[ 883874-56-4 ]
[ 29886-64-4 ]
N-(4-(4-(2-fluorophenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74.9%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 1h;	General procedure for the synthesis of compound 6a-f and 7a-f General procedure: Primary amines 5a-f (1 equiv),4-(thien-3-yl)benzoic acid (0.8 equiv) or 4-(1,3-thiazol-4-yl)benzoic acid (0.8 equiv) weredissolved in CH2Cl2. To the solution, EDC (1.2 equiv) and HOBt hydrate (1.2 equiv) wasadded at 0 and stirred at room temperature for 1 h. The crude mixture was washedwith saturated NaHCO3 solution and brine. The organic layer was dried over Na2SO4 andconcentrated. The product was purified by flash column chromatography on silica gel byelution with a 0-10 % gradient of methanol in CH2Cl2 and converted to the correspondinghydrochloride salt.N-(4-(4-(2-Fluorophenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide (6a). Following thegeneral procedure, 6a (100 mg, 74.9%) was obtained as a white solid: 1H NMR (CDCl3, 500MHz) δ 1.66-1.73 (m, 4H), 2.48 (t, J = 10.0 Hz, 2H), 2.64 (s, 4H), 3.09 (s, 4H), 3.50 (dd, J =10.0, 5.0 Hz, 2H), 6.74 (br, 1H), 6.87-6.94 (m, 2H), 6.98-7.02 (m, 2H), 7.39-7.41 (m, 2H), 7.50-7.51 (m, 1H), 7.63 (d, J = 10.0 Hz, 2H), 7.80 (d, J = 5.0 Hz, 2H); 13C NMR (CDCl3, 125 MHz)δ 167.3, 156.7, 154.7, 141.2, 140.0, 138.6, 133.4, 127.6, 126.6, 126.4, 126.1, 124.4, 122.5, 121.4,118.9, 116.2, 116.0, 58.0, 53.2, 50.3, 50.2, 39.9, 27.4, 24.3; LC-MS (ESI) m/z: 438.23 [M+H].