N-Formylmorpholine → Morpholinium, 4-(chloromethylene)-, chloride

N-Formylmorpholine (7.58 g) dissolved in anhydrous ethyl ether (200 ml) is reacted with oxalyl chloride (8.02 g) under stirring at room temperature for 20 hours. The precipitate is filtered, washed with anhydrous ethyl ether and dried in vacuo at room temperature for 1 hour to yield 8.9 g of 4-chloromethylene-morpholinium chloride. This compound (5.47 g) is added portionwise at -15°60 C. to a stirred solution of 3-(8-amino-1,4-dihydro-1-phenyl-[1]-benzothiopyrano[4,3-c]pyrazol-3-yl)-2-cyano-3-oxo-N-phenyl-propanamide (3 g) in anhydrous tetrahydrofuran (130 ml) containing triethylamine (8.96 ml). The reaction mixture is kept under stirring at -15° C. for 2 hours and then at about 0° C. for 2 hours again. Finally it is diluted with ice water and acidified to pH 4 with citric acid. The precipitate is filtered, fired in vacuo at 50° C. and then purified over a SiO2 column using chloroform/methanol30% NH4OH 85/12/0.5 as eluent. The recovered product is crystallized from methanol to yield 1.4 g of 2-cyano-3(1,4-dihydro-8-morpholinomethyleneamino-1-phenyl-[1]-benzothiopyrano[4,3-c]pyrazol-3-yl)-3-oxo-N-phenyl-propanamide, m.p. 205°-210° C.

1. filtrationThe precipitate is filtered
2. washwashed with anhydrous ethyl ether
3. customdried in vacuo at room temperature for 1 hour

ORD record

ord-f0c026073b0d4012aae3083bcb867fc9

Source dataset

uspto-grants-1992_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05166152