Dimethylformamide → HCID 68438470, compound

Combination of the starting Benzyl-hydrazine 136 with Oxo-acetic acid ethyl ester 137 gives rise to intermediate (Benzyl-hydrazono)-acetic acid ethyl ester 138, which is chlorinated by treatment with N-chloromethyl succinamide or tertiary butoxy chloride to form intermediate 139. The combination of Intermediate 139 with vinyl benzene 140 forms the ester intermediate 1-Benzyl-5-phenyl-4,5-dihydro-1H-pyrazole-3-carboxylic acid ethyl ester 141. Saponification of the ester intermediate 141 gives rise to intermediate 1-Benzyl-5-phenyl-4,5-dihydro-1H-pyrazole-3-carboxylic acid 142 that gives rise to the cyanoamine intermediate 143 when heated to high temperatures in anhydrous dimethylformamide. Upon further reaction of intermediate 143 with diethyl oxalate 144 affords the intermediate 2,3-dioxo-4-cyanopyrrolidine 145, which forms intermediate 1-Benzyl-4-hydroxy-5-oxo-2-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid amide 146 under acidic conditions and an amino group replaces the OH group forming intermediate 4-Amino-1-benzyl-5-oxo-2-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid amide 147. Treatment of Intermediate 147 with dimethylformamide and sodium nitrite forms intermediate 1-Benzyl-4-imino-5-oxo-2-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylic acid amide 148 and a combination with compound But-2-ynedioic acid diethyl ester 149 forms an intermediate 7-Benzyl-9-carbamoyl-6-oxo-8-phenyl-1,2,7-triaza-spiro[4.4]nona-1,3,8-triene-3,4-dicarboxylic acid diethyl ester 150, which converts to intermediate 6-Benzyl-4-carbamoyl-7-oxo-5-phenyl-6,7-dihydro-pyrazolo[1,5-c]pyrimidine-2,3-dicarboxylic acid diethyl ester 151. Reflux of intermediate 151 in the presence of the acid gives rise to intermediate 6-Benzyl-7-oxo-5-phenyl-6,7-dihydro-pyrazolo[1,5-c]pyrimidine-4-carboxylic acid amide 152. Heating formic acid and ammonium ion mixture in methanol and 10% Pd—C to reflux eliminates the benzyl group forming intermediate 7-Oxo-5-phenyl-6,7-dihydro-pyrazolo[1,5-c]pyrimidine-4-carboxylic acid amide 153. Reflux of 153 in phosphorous oxychloride forms intermediate 7-Chloro-5-phenyl-pyrazolo[1,5-c]pyrimidine-4-carbonitrile 154 and treatment with the appropriate amine represented as Y—NH2 results in a substitution of the chloride ion of 154 with the described amine derivative intermediate 155. Treatment of 155 with NBS forms target compound 7-Amino derivative-3-bromo-5-phenyl-pyrazolo[1,5-c]pyrimidine-4-carbonitrile 156.

ORD record

ord-8058ce19b68e44e9abb0e2bf68cebcfe

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07700773B2