Alfuzosin → 3-[(4-Amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propanenitrile

HRID 1020711Notes

Reaction equation

HRID 1020711 reaction equation
[CH3:1][N:2]([C:14]1[N:23]=[C:22]([NH2:24])[C:21]2[C:16](=[CH:17][C:18]([O:27][CH3:28])=[C:19]([O:25][CH3:26])[CH:20]=2)[N:15]=1)[CH2:3][CH2:4][CH2:5][NH:6]C(C1OCCC1)=O.NC1C2C(=CC(OC)=C(OC)C=2)N=C(Cl)N=1.CNCCC#N>C(O)CC(C)C>[NH2:24][C:22]1[C:21]2[C:16](=[CH:17][C:18]([O:27][CH3:28])=[C:19]([O:25][CH3:26])[CH:20]=2)[N:15]=[C:14]([N:2]([CH2:3][CH2:4][C:5]#[N:6])[CH3:1])[N:23]=1

Participants

5

Reactant 3

HCID 2092AlfuzosinHCID 69656Propanenitrile, 3-(methylamino)-HCID 902352-Chloro-6,7-dimethoxy-4-quinazolinamine

Product 1

HCID 135447313-[(4-Amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propanenitrile

Reagents, catalysts & solvents 1

HCID 31260Isoamyl AlcoholSolvent

Procedure

The patent 007' teaches the preparation of alfuzosin or a salt thereof by reacting 4-amino-2-chloro-6,7-dimethoxy quinazoline of formula (II) with 3-methylaminopropionitrile of formula (III) in the presence of isoamyl alcohol to obtain N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methyl-2-cyanoethylamine of formula (IV) which is further hydrogenated in the presence of Raney-Nickel using 15% ammoniacal ethanol by applying 80 Kg pressure at 70° C. for 96 hours to obtain N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methylpropylenediamine of formula (V) which is then converted to the hydrochloride salt. The obtained N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methylpropylenediamine hydrochloride is then treated with carbonyldiimidazole-activated tetrahydrofuroic acid by adding a diamine compound in the presence of carbonyldiimidazole to obtain alfuzosin base which is then converted into alfuzosin hydrochloride salt.

Sources & evidence

ORD record
ord-99a0d84d34804700889811d18f49f5bb
Source dataset
uspto-grants-2014_05
Patent number
US08716476B2

Reaction notes

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