3-Acetylpyridine → 1-(3-Pyridyl)-3-(dimethylamino)-2-propen-1-one

HRID 2243399Notes

Reaction equation

HRID 2243399 reaction equation
Cl.CC1C=CC([N+]([O-])=O)=CC=1NC(N)=N.[N+]([O-])(O)=O.CC1C=CC([N+]([O-])=O)=CC=1NC(N)=N.[C:34]([C:37]1[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=1)(=[O:36])[CH3:35].CO[CH:45](OC)[N:46]([CH3:48])[CH3:47]>>[CH3:45][N:46]([CH3:48])[CH:47]=[CH:35][C:34]([C:37]1[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=1)=[O:36]

Participants

5

Reactant 4

HCID 95893-AcetylpyridineHCID 78373Dimethylformamide dimethyl acetalHCID 178426709HCID 178426709, compoundHCID 178426711HCID 178426711, compound

Product 1

HCID 5670331-(3-Pyridyl)-3-(dimethylamino)-2-propen-1-one

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-36e1fc3753654e27907a9460ef9bd8bd
Source dataset
uspto-grants-2010_03
Patent number
US07674901B2

Reaction notes

Loading…