1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-({(2S,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrolidin-2-yl}methyl)-N-[(3-phenyl-1H-1,2,4-triazol-5-yl)methyl]benzamide

HRID 1911848Notes

Reaction equation

HRID 1911848 reaction equation
C(OC([N:8]1[C@@H:12]([C@H:13]([OH:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:11][CH2:10][C@H:9]1[CH2:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=1)=O)(C)(C)C.[C:31]1([C:37]2[N:41]=[C:40]([CH2:42][NH2:43])[NH:39][N:38]=2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>CN(C)C=O>[OH:20][C@H:13]([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C@@H:12]1[NH:8][C@H:9]([CH2:21][C:22]2[CH:30]=[CH:29][C:25]([C:26]([NH:43][CH2:42][C:40]3[NH:39][N:38]=[C:37]([C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:41]=3)=[O:27])=[CH:24][CH:23]=2)[CH2:10][CH2:11]1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 26249067(3-Phenyl-1H-1,2,4-triazol-5-yl)methanamineHCID 670587074-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)benzoic acid

Product 1

HCID 706558264-({(2S,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrolidin-2-yl}methyl)-N-[(3-phenyl-1H-1,2,4-triazol-5-yl)methyl]benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)benzoic acid (i-1, 0.020 g, 0.049 mmol) in N,N-dimethylformamide (0.5 ml) was added to 1-(3-phenyl-1H-1,2,4-triazol-5-yl)methanamine (0.018 g, 0.073 mmol) followed by 1-hydroxybenzotriazole (0.0099 g, 0.073 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) hydrochloride (0.014 g, 0.073 mmol) and N,N-diisopropylethylamine (0.042 ml, 0.24 mmol). The reaction mixture was stirred at ambient temperature for 4 h. The mixture was directly purified by reverse phase HPLC (TMC Pro-Pac C18; 30-100% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient). The resulting pure fractions were lyophilized overnight to give the titled compound as a white solid. LC-MS 590.2 (M+23).

Workup

  1. customThe mixture was directly purified by reverse phase HPLC (TMC Pro-Pac C18; 30-100% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient)
  2. waitThe resulting pure fractions were lyophilized overnight

Sources & evidence

ORD record
ord-3c79de5f9c704cf88132c2929ec20aca
Source dataset
uspto-grants-2013_12
Patent number
US08604038B2

Reaction notes

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