1-(3-Pyridyl)-3-(dimethylamino)-2-propen-1-one → 2-(2-Methyl-5-nitroanilino)-4-(3-pyridyl)pyrimidine

HRID 2243400Notes

Reaction equation

HRID 2243400 reaction equation
CN(C)[CH:3]=[CH:4][C:5]([C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1)=O.[N+]([O-])(O)=O.[CH3:18][C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][C:20]=1[NH:28][C:29]([NH2:31])=[NH:30]>>[N+:25]([C:22]1[CH:23]=[CH:24][C:19]([CH3:18])=[C:20]([NH:28][C:29]2[N:31]=[C:5]([C:7]3[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=3)[CH:4]=[CH:3][N:30]=2)[CH:21]=1)([O-:27])=[O:26]

Participants

3

Reactant 2

HCID 5670331-(3-Pyridyl)-3-(dimethylamino)-2-propen-1-oneHCID 178426711HCID 178426711, compound

Product 1

HCID 106861492-(2-Methyl-5-nitroanilino)-4-(3-pyridyl)pyrimidine

Procedure

The invention provides a process for preparation of imatinib base and pharmaceutically acceptable acid addition salts thereof, comprising (a) reacting 2-methyl-5-nitroaniline with cyanamide in the presence of hydrochloric acid to obtain 1-(2-methyl-5-nitrophenyl)guanidine hydrochloride; (b) converting 1-(2-methyl-5-nitrophenyl)guanidine hydrochloride to 1-(2-methyl-5-nitrophenyl)guanidine nitrate; (c) condensing 3-acetylpyridine with N,N-dimethylformamide dimethyl acetal to obtain 3-(dimethylamino)-1-(3-pyridinyl)-prop-2-en-1-one; (d) reacting 3-(dimethylamino)-1-(3-pyridinyl)-prop-2-en-1-one with 1-(2-methyl-5-nitrophenyl)guanidine nitrate to obtain N-(5-nitro-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidineamine; (e) reducing N-(5-nitro-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidineamine using hydrazine in the presence of Raney nickel to obtain N-(5-amino-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidine-amine; (f) condensing N-(5-amino-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidine-amine with 4-chloromethylbenzoyl chloride in the presence of an inorganic base to obtain 4-chloromethyl-N-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)benzamide; (g) condensing 4-chloromethyl-N-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)benzamide with an excess of N-methylpiperazine to obtain imatinib base; adding water or a mixture of water and an organic solvent; and isolating said imatinib base; and (h) optionally, converting imatinib base to a pharmaceutically acceptable acid addition salt of imatinib base.

Sources & evidence

ORD record
ord-25a66383058f4951a08e521c58e116df
Source dataset
uspto-grants-2010_03
Patent number
US07674901B2

Reaction notes

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