Potassium Carbonate → HCID 178486247, compound

Participants

Reaction Conditions

Reaction Steps

27 mg (74 μmol) of tetrabutylammonium iodide, 153 mg (1.11 mmol) of homomorpholine hydrochloride and 153 mg (1.11 mmol) of potassium carbonate are successively added to a solution of 200 mg (0.37 mmol) of an approximately 70:30 mixture of tert-butyl 3-(4-chloromethylbenzoylamino)-5-(N′-methyl-N′-phenylhydrazinocarbonyl)thieno[2,3-c]pyrazole-1-carboxylate and tert-butyl 3-(4-chloromethylbenzoylamino)-5-(N′-(4-chlorophenyl)-N′-methylhydrazinocarbonyl)-thieno[2,3-c]pyrazole-1-carboxylate in 6 mL of dimethylformamide under argon. The reaction mixture is stirred at a temperature in the region of 25° C. for 16 hours, and then poured onto ice. It is then extracted twice with a 50/50 mixture of ethyl acetate and heptane. The organic extracts are combined, dried over magnesium sulfate and then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C. The residue is dissolved in 4 mL of methanol and the solution is introduced into a microwave oven tube. The tube is stoppered and the reaction mixture is irradiated at a temperature in the region of 100° C. for 30 minutes. The reaction mixture is then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C. The residue is purified by preparative LC/MS (conditions B). 34 mg of N-[5-(N′-methyl-N′-phenylhydrazinocarbonyl)-1H-thieno[2,3-c]pyrazol-3-yl]-4-perhydro-1,4-oxazepin-4-ylmethylbenzamide are thus obtained in the form of a yellow powder melting from 174 to 179° C. LC-MS-DAD-ELSD: 505(+)=(M+H)(+). 38 mg of N-{5-[N′-(4-chlorophenyl)-N′-methylhydrazinocarbonyl]-1H-thieno[2,3-c]pyrazol-3-yl}-4-perhydro-1,4-oxazepin-4-ylmethylbenzamide are isolated in the same manner, in the form of a yellow powder. 1H NMR (400 MHz, (CD3)2SO-d6, δ in ppm): This is the salt of the expected structure, with 2.08 (m, 2H); from 3.13 to 4.07 (m, 8H); 3.18 (s, 3H); 4.50 (broad s, 2H); 6.82 (d, J=9.0 Hz, 2H); 7.25 (d, J=9.0 Hz, 2H); 7.70 (broad d, J=8.0 Hz, 2H); 8.17 (partially masked d, J=8.0 Hz, 2H); 8.18 (s, 1H); 9.75 (broad multiplet, 1H); 10.85 (s, 1H); 11.3 (s, 1H); 12.95 (very broad m, 1H).

Provenance & Evidence