Dimethylformamide → (S)-2-[3-(1H-Indol-6-yl)-phenylcarbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester

HRID 1865857Notes

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]=[C:42]2[C:38]([CH:39]=[CH:40][NH:41]2)=[CH:37][CH:36]=1.C([O-])(O)=O.[Na+].CN(C=O)C>CO>[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]=[C:42]3[C:38]([CH:39]=[CH:40][NH:41]3)=[CH:37][CH:36]=2)[CH:19]=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 mg, 0.2 mmol), 6-Bromo-1H-indole (1 eq., 49 mg), Pd[P(Ph)3]4 (5 mol %, 10 mg), in methanol (4 mL), NaHCO3 (sat. aq., 600 uL) and DMF (800 uL) was degassed and heated to 70° C. overnight in a sealed vial. The reaction was cooled, filtered and the solvents removed. The resulting mixture was redissolved in 5 ml of 90% DMF, 10% water with 0.1% TFA and purified by reverse phase HPLC to give the products. Yield 5.7 mg. MS: 440.3 (M+H). H1-NMR (DMSO-d6): δ (ppm) 11.1 (s, 1H), 10.1 (s, 1H), 8.0 (m, 1H), 7.6-7.2 (m, 12H), 7.0 (m, 2H), 6.4 (m, 1H), 5.0 (m, 2H), 4.4 (m, 1H), 3.5 (m, 1H), 2.2 (m, 1H), 1.9 (m, 3H).

Workup

temperatureThe reaction was cooled
filtrationfiltered
customthe solvents removed
dissolutionThe resulting mixture was redissolved in 5 ml of 90% DMF
custom10% water with 0.1% TFA and purified by reverse phase HPLC
customto give the products

Sources & evidence

ORD record: ord-78b33ee472024f1f9ee0d76af4735f4e
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07629340B2

Reaction notes

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