Dimethylformamide → (S)-2-(3'-Cyano-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid benzyl ester

HRID 1865864Notes

Reaction equation

[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16](=[O:33])[NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:19]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:35]1[CH:36]=[C:37]([CH:40]=[CH:41][CH:42]=1)[C:38]#[N:39].CN(C=O)C>CO.C([O-])(O)=O.[Na+]>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16](=[O:33])[NH:17][C:18]1[CH:19]=[C:20]([C:35]2[CH:42]=[CH:41][CH:40]=[C:37]([C:38]#[N:39])[CH:36]=2)[CH:21]=[CH:22][CH:23]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of (S)-2-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylcarbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester (90.4 mg, 0.20 mmol), 3-bromo-benzonitrile (37.5 mg, 0.21 mmol), and Pd[P(Ph)3]4 (15.9 mg, 6.9 mol %) in methanol (2 mL), NaHCO3 (sat. aq., 300 μL), and DMF (400 μL) was degassed and heated to 70° C. overnight in a sealed vial. The reaction was cooled, filtered, and purified by reverse phase HPLC to give the desired product. Yield 11.7 mg. MS: 426.1 (M+H+); H1 NMR (DMSO-d6): δ (ppm) 1.80-2.04 (m, 3H), 2.15-2.36 (m, 1H), 3.39-3.58 (m 2H), 4.32-4.43 (m, 1H), 4.89-5.14 (m, 2H), 7.03-8.07 (m, 13H), 10.13-10.20 (s, 1H).

Workup

temperatureThe reaction was cooled
filtrationfiltered
custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-a66380c2c58e48b4ae564e62f5140e00
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07629340B2

Reaction notes

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