Triethylamine → (2S)-1-(4-Fluoro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid [4-(4-trifluoromethyl-phenyl)-pyrimidin-2-ylmethyl]-amide

HRID 1914530Notes

Reaction equation

HRID 1914530 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([CH2:15][NH2:16])[N:10]=2)=[CH:5][CH:4]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([N:29]2[CH2:33][CH2:32][CH2:31][C@H:30]2[C:34](O)=[O:35])(=[O:28])=[O:27])=[CH:22][CH:21]=1.ON1C2C=CC=CC=2N=N1.CCN(CC)CC>CO.CN(C=O)C>[F:18][C:2]([F:1])([F:17])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([CH2:15][NH:16][C:34]([C@@H:30]3[CH2:31][CH2:32][CH2:33][N:29]3[S:26]([C:23]3[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=3)(=[O:28])=[O:27])=[O:35])[N:10]=2)=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 686685(2S)-1-(4-fluorobenzenesulfonyl)pyrrolidine-2-carboxylic acidHCID 66832336C-[4-(4-trifluoromethyl-phenyl)-pyrimidin-2-yl]-methylamine

Product 1

HCID 66832225(2S)-1-(4-Fluoro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid [4-(4-trifluoromethyl-phenyl)-pyrimidin-2-ylmethyl]-amideYield 19%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of C-[4-(4-trifluoromethyl-phenyl)-pyrimidin-2-yl]-methylamine (92 mg, 0.4 mmol), (S)-1-(4-fluoro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (99 mg, 0.4 mmol), N-(3-dimethylamniopropyl)-N′-ethylcarbodiimide hydrochloride (139 mg, 0.72 mmol), 1-hydroxybenzotriazole (98 mg, 0.73 mmol), Et3N (0.15 mL, 1.10 mmol), and DMF (2 mL) was stirred at rt for 12 hours. 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 (35 mg, 19%) of a white solid. MS (ESI): mass calcd. for C23H20F4N4O3S, 508.1; m/z found, 509.5 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 8.86 (d, J=5.3, 1H), 8.38 (d, J=8.1, 2H), 8.37-8.33 (m, 1H), 7.99-7.92 (m, 2H), 7.82 (d, J=8.2, 2H), 7.70 (d, J=5.3, 1H), 7.30-7.25 (m, 1H), 4.93-4.76 (m, 2H), 4.31-4.22 (m, 1H), 3.69 (td, J=7.3, 3.7, 1H), 3.25 (td, J=9.8, 6.7, 1H), 2.36-2.29 (m, 1H), 1.97-1.59 (m, 3H).

Workup

  1. waitAfter 12 h
  2. customresulting solution
  3. customwas purified by preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-4d3b4bac2b4f449da5a2342c2e8401d5
Source dataset
uspto-grants-2013_12
Patent number
US08614201B2

Reaction notes

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