Sodium Carbonate → (8R,9aS)-8-hydroxy-2-[5-(trifluoromethyl)pyridin-2-yl]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one

HRID 1050301Notes

Reaction equation

Cl.[OH:2][C@H:3]1[CH2:13][N:6]2[C:7](=[O:12])[CH2:8][CH2:9][NH:10][CH2:11][C@@H:5]2[CH2:4]1.Br[C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][N:16]=1.C(=O)([O-])[O-].[Na+].[Na+]>CS(C)=O>[OH:2][C@H:3]1[CH2:13][N:6]2[C:7](=[O:12])[CH2:8][CH2:9][N:10]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][N:16]=3)[CH2:11][C@@H:5]2[CH2:4]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (8R,9aS)-8-hydroxyoctahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one hydrochloride (90 mg, 0.435 mmol, Part A), 2-bromo-5-(trifluoromethyl)pyridine (148 mg, 0.635 mmol) and sodium carbonate (138 mg, 1.306 mmol) in dimethyl sulfoxide (0.4 mL) was stirred at 100° C. overnight. The mixture was purified by chromatography on silica gel (ethyl acetate/methanol=15:1) to give 135 mg (98% yield) of the titled compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.77 (m, 1H), 2.09 (m, 1 H), 2.50-2.66 (m, 2 H), 3.08 (m, 1 H), 3.35 (m, 2 H), 3.50 (m, 1 H), 3.98 (m, 2H), 4.20 (m, 1H), 4.44 (m, 1H), 4.55 (m, 1H), 4.88 (br s, 1H), 7.01 (d, J=8 Hz, 1 H), 7.81 (d, J=8 Hz, 1 H), 8.43 (s, 1H); MS (ESI) m/z 316.0 (M+H)+.

Workup

customThe mixture was purified by chromatography on silica gel (ethyl acetate/methanol=15:1)

Sources & evidence

ORD record: ord-28c602509acc48ddb97895846ef67afe
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382258B2

Reaction notes

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