Triethylamine → (1S,2S)-1-(4-Fluoro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid [1-(4'-trifluoromethyl-biphenyl-3-yl)-ethyl]-amide

HRID 1914529Notes

Reaction equation

HRID 1914529 reaction equation
Cl.[F:2][C:3]([F:20])([F:19])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C@@H:16]([NH2:18])[CH3:17])[CH:11]=2)=[CH:6][CH:5]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([S:28]([N:31]2[CH2:35][CH2:34][CH2:33][C@H:32]2[C:36](O)=[O:37])(=[O:30])=[O:29])=[CH:24][CH:23]=1.ON1C2C=CC=CC=2N=N1.CCN(CC)CC>CO.CN(C=O)C>[F:2][C:3]([F:19])([F:20])[C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C@@H:16]([NH:18][C:36]([C@@H:32]3[CH2:33][CH2:34][CH2:35][N:31]3[S:28]([C:25]3[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=3)(=[O:30])=[O:29])=[O:37])[CH3:17])[CH:11]=2)=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 686685(2S)-1-(4-fluorobenzenesulfonyl)pyrrolidine-2-carboxylic acidHCID 66832512(5)-1-(4'-Trifluoromethyl-biphenyl-3-yl)ethylamine hydrochloride

Product 1

HCID 49832576(1S,2S)-1-(4-Fluoro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid [1-(4'-trifluoromethyl-biphenyl-3-yl)-ethyl]-amideYield 54%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (5)-1-(4′-trifluoromethyl-biphenyl-3-yl)ethylamine hydrochloride (75 mg, 0.25 mmol), (S)-1-(4-fluoro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (68 mg, 0.25 mmol), N-(3-dimethylamniopropyl)-N′-ethylcarbodiimide hydrochloride (71 mg, 0.37 mmol), 1-hydroxybenzotriazole (50 mg, 0.37 mmol) and DMF (2 mL) was added Et3N (0.10 mL, 0.75 mmol). After 12 h, MeOH (0.5 mL) was added to the reaction mixture and resulting solution was purified by preparative reverse-phase HPLC to afford (70 mg, 54%) of a white solid. MS (ESI): mass calcd. for C26H24F4N2O3S, 520.1; m/z found, 521.1 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 7.93-7.87 (m, 2H), 7.79 (d, J=8.0, 2H), 7.73-7.66 (m, 3H), 7.54 (d, J=7.6, 1H), 7.49 (t, J=7.6, 1H), 7.44 (d, J=7.6, 1H), 7.35 (d, J=8.0, 1H), 7.30-7.23 (m, J=8.7, 1H), 5.27-5.11 (m, 1H), 4.11 (dd, J=8.9, 3.1, 1H), 3.71-3.60 (m, 1H), 3.26-3.15 (m, 1H), 2.28-2.17 (m, 1H), 1.91-1.75 (m, 1H), 1.74-1.64 (m, 2H), 1.60 (d, J=7.0, 3H).

Workup

  1. customresulting solution
  2. customwas purified by preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-b78cb65b2eca415993a5cb6df7426d46
Source dataset
uspto-grants-2013_12
Patent number
US08614201B2

Reaction notes

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