反应详情

Ten grams of 3,3a,4,5,6,7-hexahydro-3-phenyl-7-(phenylmethylene)-2-(2,2,2-trifluoroethyl)-2H-pyrazolo[4,3-c]-pyridine, monohydrochloride (see Example 2) is reacted with 8.2 g of cyanamide in 350 ml of ethanol at reflux temperature for 24 hours. The bulk of ethanol is removed on a rotary evaporator and the residue (which does not crystallize) is converted to 10.8 g of the free base (using sodium hydroxide and chloroform extractions); melting point 155°-157° C (foaming), sintering at 120° C. The base is dissolved in 400 ml of dichloromethane, treated with 5 ml of 6.1 N alcoholic hydrogen chloride, and the solvents removed on a rotary evaporator. The foamy residue (11.7 g) is stirred with 50 ml of water and 150 ml of ether. The material becomes gummy, then slowly crystallizes on cooling in ice-water, continued stirring, and rubbing. After standing in the cold for about 16 hours, the product is filtered, washed with ether, and air-dried, yielding 5.3 g of material; melting point 222°-225° C, sintering at 210° C. Crystallization from acetonitrile (dissolved in 200 ml of boiling solvent, then concentrated to approximately 100 ml; crystallization proceeeds very slowly while standing in the cold for several days) yields 3.0 g of product; melting point 230°-232° C, sintering at 223° C.

1. temperatureat reflux temperature for 24 hours
2. customThe bulk of ethanol is removed on a rotary evaporator
3. customthe residue (which does not crystallize)
4. customsintering at 120° C
5. dissolutionThe base is dissolved in 400 ml of dichloromethane
6. additiontreated with 5 ml of 6.1 N alcoholic hydrogen chloride
7. customthe solvents removed on a rotary evaporator
8. customslowly crystallizes
9. temperatureon cooling in ice-water
10. stirringcontinued stirring
11. customcold for about 16 hours
12. filtrationthe product is filtered
13. washwashed with ether
14. customair-dried