1,2-Dichloroethane → N-{[5-(3-{[(3S)-3-methyl-1-piperazinyl]methyl}phenyl)-2-thienyl]methyl}-3-(4-piperidinylmethyl)benzamide

HRID 2080335Notes

Reaction equation

HRID 2080335 reaction equation
CC(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]2[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=2)[C:18]([OH:20])=O)[CH2:10][CH2:9]1)=O)(C)C.[NH2:24][CH2:25][C:26]1[S:30][C:29]([C:31]2[CH:32]=[C:33]([CH2:37][N:38]3[CH2:43][CH2:42][N:41](C(OC(C)(C)C)=O)[C@@H:40]([CH3:51])[CH2:39]3)[CH:34]=[CH:35][CH:36]=2)=[CH:28][CH:27]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C([O-])([O-])=O.[Na+].[Na+].C(O)(C(F)(F)F)=O>C(Cl)(Cl)Cl>[CH3:51][C@@H:40]1[NH:41][CH2:42][CH2:43][N:38]([CH2:37][C:33]2[CH:32]=[C:31]([C:29]3[S:30][C:26]([CH2:25][NH:24][C:18](=[O:20])[C:17]4[CH:21]=[CH:22][CH:23]=[C:15]([CH2:14][CH:11]5[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]5)[CH:16]=4)=[CH:27][CH:28]=3)[CH:36]=[CH:35][CH:34]=2)[CH2:39]1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 757711-HydroxybenzotriazoleHCID 450739593-((1-(tert-Butoxycarbonyl)piperidin-4-yl)methyl)benzoic acidHCID 577367031,1-dimethylethyl (2S)-4-({3-[5-(aminomethyl)-2-thienyl]phenyl)methyl)-2-methyl-1-piperazinecarboxylate

Product 1

HCID 57736706N-{[5-(3-{[(3S)-3-methyl-1-piperazinyl]methyl}phenyl)-2-thienyl]methyl}-3-(4-piperidinylmethyl)benzamideYield 50%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of 3-[(1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-piperidinyl)methyl]benzoic acid (128 mg, 0.40 mmol) in CHCl3 (2.0 mL) was added 1,1-dimethylethyl (2S)-4-({3-[5-(aminomethyl)-2-thienyl]phenyl)methyl)-2-methyl-1-piperazinecarboxylate (160 mg, 0.40 mmol), TEA (0.1 ml, 0.7 mmol), EDC (115 mg, 0.6 mmol) and HOBt (59 mg, 0.44 mmol). The reaction mixture was stirred at room temperature for 2 h, followed by addition of 0.5 mL of saturated Na2CO3. The organic layer was isolated via a hydrophobic frit followed by addition of 0.5 mL of TFA, and stirred at room temperature for 1 h. After removal of the solvent, the residue was purified by Gilson reverse phase HPLC, eluting with acetonitrile/water/0.1% TFA (10/90 to 70/30, v/v, over 12 min), to give the title compound (100 mg, 50%). LC/MS: m/z, 503 (M+H), 1.22 min.

Workup

  1. customThe organic layer was isolated via a hydrophobic frit
  2. stirringstirred at room temperature for 1 h
  3. customAfter removal of the solvent
  4. customthe residue was purified by Gilson reverse phase HPLC
  5. washeluting with acetonitrile/water/0.1% TFA (10/90 to 70/30, v/v, over 12 min)

Sources & evidence

ORD record
ord-5e8b47e6222841c5bf7aa047605a6cea
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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