4-Bromo-2,6-difluorophenyl isocyanate → N-(4-bromo-2,6-difluorophenyl)-2-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetyl}hydrazinecarboxamide

HRID 2405352Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([F:12])[C:5]([N:9]=[C:10]=[O:11])=[C:6]([F:8])[CH:7]=1.[CH:13]1([C:16]([N:18]2[CH2:22][CH2:21][C@@H:20]([CH2:23][C:24]([NH:26][NH2:27])=[O:25])[CH2:19]2)=[O:17])[CH2:15][CH2:14]1>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([F:12])[C:5]([NH:9][C:10]([NH:27][NH:26][C:24](=[O:25])[CH2:23][C@@H:20]2[CH2:21][CH2:22][N:18]([C:16]([CH:13]3[CH2:15][CH2:14]3)=[O:17])[CH2:19]2)=[O:11])=[C:6]([F:8])[CH:7]=1

Participants

Conditions

Temperature: -78 °C

Procedure

In a round-bottom flask, 5-bromo-1,3-difluoro-2-isocyanatobenzene (1550 mg, 6.62 mmol) was dissolved in dichloromethane (10 mL) under nitrogen and cooled to −78° C. In a separate vial, 2-[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetohydrazide (1357 mg, 6.42 mmol) was dissolved in 10 mL of dichloromethane and then added to the cooled solution. The resultant reaction mixture was allowed to warm to room temperature and stirred for 1 h. A precipitate began to form and analysis by LCMS indicated formation of the desired product. The precipitated product was collected under vacuum filtration and washed with dichloromethane to afford the title product as a white solid (2850 mg, 99%). MS(ES)+ m/e 445.2, 447.1 [M+H]+.

Workup

additionadded to the cooled solution
customThe resultant reaction mixture
temperatureto warm to room temperature
customto form

Sources & evidence

ORD record: ord-a8700821ef7e4ebb9c2c2bf0f27057a2
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802864B2

Reaction notes

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