Imatinib → N-(4-Methyl-3-nitro-phenyl)-4-(4-methyl-piperazin-1-ylmethyl)-benzamide

HRID 1987488Notes

Reaction equation

CC1C=CC(NC(C2C=CC(CN3CCN(C)CC3)=CC=2)=O)=CC=1NC1N=CC=C(C2C=CC=NC=2)N=1.CO[C:40](=[O:55])[C:41]1[CH:46]=[CH:45][C:44]([CH2:47][N:48]2[CH2:53][CH2:52][N:51]([CH3:54])[CH2:50][CH2:49]2)=[CH:43][CH:42]=1.[N+:56]([C:59]1[CH:60]=[C:61]([CH:63]=[CH:64][C:65]=1[CH3:66])[NH2:62])([O-:58])=[O:57]>>[CH3:66][C:65]1[CH:64]=[CH:63][C:61]([NH:62][C:40](=[O:55])[C:41]2[CH:42]=[CH:43][C:44]([CH2:47][N:48]3[CH2:49][CH2:50][N:51]([CH3:54])[CH2:52][CH2:53]3)=[CH:45][CH:46]=2)=[CH:60][C:59]=1[N+:56]([O-:58])=[O:57]

Participants

Reactant 3

HCID 5291Imatinib

HCID 83904-Methyl-3-nitroaniline

HCID 782222Methyl 4-((4-methylpiperazin-1-yl)methyl)benzoate

Product 1

HCID 29984087N-(4-Methyl-3-nitro-phenyl)-4-(4-methyl-piperazin-1-ylmethyl)-benzamide

Procedure

U.S. Pat. No. 5,521,184 and WO 03/066613 describe synthetic routes for preparing imatinib. One synthetic process, depicted in Scheme 1, involves reacting 4-(4-methyl-piperazin-1-ylmethyl)-benzoic acid methyl ester with 3-nitro-4-methyl-aniline to obtain N-(4-methyl-3-nitrophenyl)-4-(4-methyl-piperazin-1-ylmethyl)-benzamide, which is subsequently reduced to obtain N-(3-amino-4-methyl-phenyl)-4-(4-methyl-piperazin-1-ylmethyl)-benizamide. The latter is reacted with cyanamide (NH2CN) in a mixture of concentrated hydrochloric acid solution and n-butanol to produce N-(3-guanidino-4-methyl-phenyl)-4-(4-methyl-piperazin-1-ylmethyl)-benzamide, which is subsequently reacted with 3-dimethylamino-1-pyridin-3-yl-propenone to obtain imatinib.

Sources & evidence

ORD record: ord-96dd1705c16f4d86a71c01c50fe83064
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07550591B2

Reaction notes

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