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

HRID 1865869Notes

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:44]=[CH:45][CH:46]=1)[C:38]([NH:40][CH:41]1[CH2:43][CH2:42]1)=[O: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:45]2[CH:46]=[CH:35][CH:36]=[C:37]([C:38](=[O:39])[NH:40][CH:41]3[CH2:43][CH2:42]3)[CH:44]=2)[CH:21]=[CH:22][CH:23]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=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 (93.7 mg, 0.21 mmol), 3-bromo-N-cyclopropyl-benzamide (50.0 mg, 0.21 mmol), and Pd[P(Ph)3]4 (12.8 mg, 5.3 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 5.1 mg. MS: 484.2 (M+H+); H1 NMR (DMSO-d6): δ (ppm) 0.54-0.78 (m, 4H), 1.77-2.05 (m, 3H), 2.14-2.37 (m, 1H), 2.80-2.94 (m, 1H), 3.40-3.58 (m, 2H), 4.30-4.44 (m, 1H), 4.38-5.14 (m, 2H), 7.00-8.07 (m, 13H), 8.49-8.59 (m, 1H), 10.10-10.09 (s, 1H).

Workup

temperatureThe reaction was cooled
filtrationfiltered
custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-fd1a28d481b843928b6bf0d14d1242f7
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07629340B2

Reaction notes

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