Hydrochloric Acid → HCID 178422944, compound

Temperature

40 °C

To a solution of 5,7-dichloro-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}pyrazolo[1,5-a]pyrimidine (1.9 g, 5.28 mmol) in water (10.0 mL) and tetrahydrofuran (40 mL) stirred at 0° C. was added a solution of 1M NaOH solution (5.28 g, 13.2 mmol) in dropwise during 5 min. The reaction mixture was stirred at 40° C. for 1 hour. Excess solvent was removed. The residue was dissolved with ethyl acetate (100 mL) and water (25 mL). The pH of aqueous layer was adjusted to pH 7. Two layers were separated. Aqueous Layer was extracted with ethyl acetate (50 mL×2). Combined layers were dried and concentrated to dryness. The product was obtained and used in next step. (1.64 g, 91%); LC/MS: MS (ES+) m/e 342 (MH+). To a solution of 5-chloro-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}pyrazolo[1,5-a]pyrimidin-7(4H)-one (1.21 g, 3.54 mmol) in ethanol (3 mL) stirred under nitrogen at 20° C. was added neat morpholine (0.925 g, 10.62 mmol). The reaction vessel was sealed and irradiated (microwave) at 145° C. for 4 hr. Reaction mixture diluted with ethyl acetate (50 mL) and water (15 mL). The pH of aqueous layer was adjusted with conc. HCl solution to 5. Two layers were separated. Aqueous layer was extracted with ethyl acetate (50 mL) again. Combined layers were dried and concentrated. The crude material was then purified with column chromatography (silica gel, CH3OH/DCM 0-10%). Desired product was obtained and used in next step. (520 mg, 37%); LC/MS: MS (ES+) m/e 393 (MH+).

1. customExcess solvent was removed
2. dissolutionThe residue was dissolved with ethyl acetate (100 mL) and water (25 mL)
3. customTwo layers were separated
4. extractionAqueous Layer was extracted with ethyl acetate (50 mL×2)
5. customCombined layers were dried
6. concentrationconcentrated to dryness
7. customThe product was obtained
8. customThe reaction vessel was sealed
9. customirradiated (microwave) at 145° C. for 4 hr
10. customReaction mixture
11. customTwo layers were separated
12. extractionAqueous layer was extracted with ethyl acetate (50 mL) again
13. customCombined layers were dried
14. concentrationconcentrated
15. customThe crude material was then purified with column chromatography (silica gel, CH3OH/DCM 0-10%)

ORD record

ord-306e4153664a46cdb9f4c01b647565b3

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096605B2