Hydrochloric Acid → HCID 178426709, compound

HRID 2243398Notes

Reaction equation

HRID 2243398 reaction equation
CC1C=CC(NC(C2C=CC(CN3CCN(C)CC3)=CC=2)=O)=CC=1[NH:8][C:9]1N=CC=C(C2C=CC=NC=2)[N:14]=1.[CH3:38][C:39]1[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][C:40]=1[NH2:41].N#CN.[ClH:52]>>[ClH:52].[CH3:38][C:39]1[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][C:40]=1[NH:41][C:9]([NH2:14])=[NH:8]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 5291ImatinibHCID 74442-Methyl-5-NitroanilineHCID 9864Cyanamide

Product 1

HCID 178426709HCID 178426709, compound

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.

Workup

  1. customThe invention provides a process

Sources & evidence

ORD record
ord-d371c671aa3a4cc98ca9607af812bc0f
Source dataset
uspto-grants-2010_03
Patent number
US07674901B2

Reaction notes

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