Cyclopropylamine → 4-bromo-N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)picolinamide

HRID 1040252Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH:17]=[N:18][CH:19]3[CH2:21][CH2:20]3)[CH:12]=2)=[O:9])[CH:3]=1.C1(C)C(S([CH2:31][N+:32]#[C-:33])(=O)=O)=CC=CC=1.C1(N)CC1>C(COC)OC.CO>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]3[N:18]([CH:19]4[CH2:21][CH2:20]4)[CH:33]=[N:32][CH:31]=3)[CH:12]=2)=[O:9])[CH:3]=1

Participants

Conditions

Temperature: 52 °C

Procedure

To a solution of 4-bromo-N-(3-((cyclopropylimino)methyl)phenyl)-picolinamide (970 mg, 2.83 mmol) in dimethoxyethane/methanol (2:1, 0.1M) were added toluenesulfonylmethyl isocyanide (1.10 g, 5.65 mmol) and cyclopropylamine (392 μL, 5.65 mmol). The reaction mixture was stirred for 14 hours at 52° C., and additional toluenesulfonylmethyl isocyanide (550 mg, 2.83 mmol) was added. The reaction mixture was stirred an additional 6 hours, the solvent removed under reduced pressure, concentrated, and the residue purified by flash chromatography (2-8% methanol in methylene chloride) to afford 110 mg of 4-bromo-N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)picolinamide. M+1=383.1

Workup

stirringThe reaction mixture was stirred an additional 6 hours
customthe solvent removed under reduced pressure
concentrationconcentrated
customthe residue purified by flash chromatography (2-8% methanol in methylene chloride)

Sources & evidence

ORD record: ord-3a84a9d7dafb4ad4acd1f3c580b621c8
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08552196B2

Reaction notes

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