Dimethylformamide → (S)-2-{4'-[(Cyclopropanecarbonyl-amino)-methyl]-biphenyl-3-ylcarbamoyl}-pyrrolidine-1-carboxylic acid benzyl ester

HRID 1865866Notes

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:47]=[CH:46][C:38]([CH2:39][NH:40][C:41]([CH:43]2[CH2:45][CH2:44]2)=[O:42])=[CH:37][CH:36]=1.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:47]=[CH:46][C:38]([CH2:39][NH:40][C:41]([CH:43]3[CH2:45][CH2:44]3)=[O:42])=[CH:37][CH:36]=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 (93.8 mg, 0.21 mmol), cyclopropanecarboxylic acid 4-bromo-benzylamide (50.6 mg, 0.20 mmol), and Pd[P(Ph)3]4 (13.7 mg, 5.7 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 15.0 mg. MS: 498.2 (M+H+); H1 NMR (DMSO-d6): δ (ppm) 0.61-0.79 (m, 4H), 1.56-1.69 (m, 3H), 2.11-2.35 (m, 1H), 3.38-3.59 (m, 2H), 4.25-4.43 (m, 3H), 4.89-5.15 (m, 2H), 7.00-7.65 (m, 12H), 7.85-7.95 (m, 1H), 8.51-8.63 (m, 1H), 10.07-10.16 (s, 1H).

Workup

temperatureThe reaction was cooled
filtrationfiltered
custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-1b9f0fd07264456d8d03a1f6778e9c61
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07629340B2

Reaction notes

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