Dimethylformamide → (S)-2-(3-Benzothiazol-6-yl-phenylcarbamoyl)-pyrrolidine-1-carboxylic acid benzyl ester

HRID 1865862Notes

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:43]=[CH:42][C:38]2[N:39]=[CH:40][S:41][C:37]=2[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:23]=[CH:22][CH:21]=[C:20]([C:35]2[CH:43]=[CH:42][C:38]3[N:39]=[CH:40][S:41][C:37]=3[CH:36]=2)[CH:19]=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 (74 mg, 0.16 mmol), 6-bromo-benzothiazole (34.9 mg, 0.16 mmol), and Pd[P(Ph)3]4 (12.1 mg, 6.4 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 5.6 mg. MS: 458.1 (M+H+); H1 NMR (DMSO-d6): δ (ppm) 1.18-1.25 (m, 2H), 1.76-2.00 (m, 3H), 2.10-2.34 (m, 1H), 4.28-4.40 (m, 1H), 4.87-5.10 (m, 2H), 7.00-7.56 (m, 7H), 7.68-7.66 (m, 1H), 7.97-8.15 (m, 2H), 8.33-8.39 (m, 1H), 9.35-9.39 (s, 1H), 10.09-10.16 (s, 1H).

Workup

temperatureThe reaction was cooled
filtrationfiltered
custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-7681da30217f4731bdc5b07bbd98c182
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07629340B2

Reaction notes

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