Sodium Cyanide → 4-[(1-Cyanocyclobutyl)amino]-2-fluoro-N-methylbenzamide
Reaction equation
[F:1][C:2]1[CH:11]=[C:10]([NH2:12])[CH:9]=[CH:8][C:3]=1[C:4]([NH:6][CH3:7])=[O:5].[C-:13]#[N:14].[Na+].[C:16]1(=O)[CH2:19][CH2:18][CH2:17]1>>[C:13]([C:16]1([NH:12][C:10]2[CH:9]=[CH:8][C:3]([C:4]([NH:6][CH3:7])=[O:5])=[C:2]([F:1])[CH:11]=2)[CH2:19][CH2:18][CH2:17]1)#[N:14]Participants
Procedure
A solution of 2,4-difluoro-benzoylchloride D in a solution of methylamine and tetrahydrofuran (THF) is allowed to react to produce 2,4-difluoro-N-methylbenzamide M (quantitative yield). The 2,4-difluoro-N-methylbenzamide M is mixed with in a solution of acetonitrile and 4-methoxy-benzenemethanamine and heated in a microwave for 20 minutes at 190° C. to produce 2-fluoro-4-(4-methoxybenzylamino)-N-methylbenzamide S (yield of 40%). The 2-fluoro-4-(4-methoxybenzylamino)-N-methylbenzamide S is reacted in a solution of dichloromethane and trifluoroacetic acid to produce 2-fluoro-4-amino-N-methylbenzamide T (yield greater than 95%). The 2-fluoro-4-amino-N-methylbenzamide T is reacted with a solution of sodium cyanide and cyclobutanone to produce 4-(1-cyanocyclobutylamino)-2-fluoro-N-methylbenzamide B.
Sources & evidence
- ORD record
- ord-c2df5a9fb3f94770a01f60ae7819cc0b
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08445507B2
Reaction notes
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