Diisopropylethylamine → 1-((1S,3R)-3-benzyloxycarbonyl-1-biphenyl-4-ylmethyl-butylcarbamoyl)-1H-pyrazole-3-carboxylic acid

HRID 2384027Notes

Reaction equation

HRID 2384027 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([C:6]([OH:8])=[O:7])=[N:2]1.C(N(C(C)C)CC)(C)C.[CH2:18]([O:25][C:26](=[O:47])[C@H:27]([CH3:46])[CH2:28][C@H:29]([N:43]=[C:44]=[O:45])[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:33][CH:32]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C=O)C>[CH2:18]([O:25][C:26]([C@H:27]([CH3:46])[CH2:28][C@H:29]([NH:43][C:44]([N:1]1[CH:5]=[CH:4][C:3]([C:6]([OH:8])=[O:7])=[N:2]1)=[O:45])[CH2:30][C:31]1[CH:32]=[CH:33][C:34]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)=[CH:35][CH:36]=1)=[O:47])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86648208(2R,4S)-5-biphenyl-4-yl-4-isocyanato-2-methyl-pentanoic acid benzyl esterHCID 178524567HCID 178524567, compound

Product 1

HCID 675058851-((1S,3R)-3-benzyloxycarbonyl-1-biphenyl-4-ylmethyl-butylcarbamoyl)-1H-pyrazole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Next, to a solution of 1H-pyrazole-3-carboxylic acid (20.5 mg, 0.183 mmol) in DMF (1 mL) is added diisopropylethylamine (0.032 mL, 0.183 mmol). After 15 min a solution of the above (2R,4S)-5-biphenyl-4-yl-4-isocyanato-2-methyl-pentanoic acid benzyl ester in DMF (1 mL) is added dropwise and the mixture is stirred at room temperature for 18 hours. The mixture is purified by preparative HPLC using a gradient of 10% MeCN to 100% MeCN (0.1% TFA). Lyophilization of the appropriate fractions furnishes 1-((1S,3R)-3-benzyloxycarbonyl-1-biphenyl-4-ylmethyl-butylcarbamoyl)-1H-pyrazole-3-carboxylic acid.

Workup

  1. customThe mixture is purified by preparative HPLC

Sources & evidence

ORD record
ord-1266020b3a104f08abd4faad23580148
Source dataset
uspto-grants-2012_09
Patent number
US08263629B2

Reaction notes

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