Potassium Carbonate → HCID 178464057, compound

Temperature

25 °C

27 mg (74 μmol) of tetrabutylammonium iodide, 156 μL (1.11 mmol) of N,N-diethylethylenediamine 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). The fractions containing the expected products are combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is repurified by chromatography on a cartridge of 4 g of silica gel (0.035-0.060 mm), eluting with a dichloromethane/methanol mixture and then with a mixture of dichloromethane and methanol/28% aqueous ammonia (85/15 by volume). The fractions containing the expected products are combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 8 mg of 4-[(2-diethylaminoethylamino)methyl]-N-[5-(N′-methyl-N′-phenylhydrazinocarbonyl)-1H-thieno[2,3-c]pyrazol-3-yl]benzamide are thus obtained in the form of a pale yellow powder melting from 143 to 150° C. LC-MS-DAD-ELSD: 520(+)/ . . . =(M+H)(+)/ . . . (1 Cl).

1. additionpoured onto ice
2. extractionIt is then extracted twice with a 50/50 mixture of ethyl acetate and heptane
3. dry with materialdried over magnesium sulfate
4. concentrationconcentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C
5. dissolutionThe residue is dissolved in 4 mL of methanol
6. additionthe solution is introduced into a microwave oven tube
7. customthe reaction mixture is irradiated at a temperature in the region of 100° C. for 30 minutes
8. concentrationThe reaction mixture is then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C
9. customThe residue is purified by preparative LC/MS (conditions B)
10. additionThe fractions containing the expected products
11. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
12. customThe residue is repurified by chromatography on a cartridge of 4 g of silica gel (0.035-0.060 mm)
13. washeluting with a dichloromethane/methanol mixture
14. additionwith a mixture of dichloromethane and methanol/28% aqueous ammonia (85/15 by volume)
15. additionThe fractions containing the expected products
16. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

ORD record

ord-bc0a93b471064c3aad6053fa0bcf408d

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07595320B2