Phosphorus oxychloride → 7-Chloro-2-(1,1-difluoroethyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine

This intermediate was synthesized by suspending Intermediate 2 in phosphorus oxychloride (ALDRICH, 21.98 ml, 236 mmol) was heating the mixture under reflux for 2 h, the starting material dissolved meanwhile. An aliquot of the reaction was partitioned between NaCO3 10% aq. (1 mL) and DCM (1 mL) and the organic phase was checked by TLC (Hexane/AcOEt 6/4) showing the reaction was complete. The reaction mixture was slowly added to a mixture of water and ice. The solution was neutralized with 10% aq. Na2CO3 (800 mL approx.) and product was extracted with DCM (250 mL). The aqueous layer was further extracted with DCM (2×150 mL) and the combined organic layers were washed with water (200 mL), then with brine (200 mL) and dried over MgSO4. Solvent was removed under reduced pressure. The crude product was purified (silica gel column, eluting with Hexane/AcOEt mixtures from 100:0 to 50:50%) and Intermediate 3 was obtained as a white solid.

1. customThis intermediate was synthesized
2. temperaturewas heating the mixture
3. temperatureunder reflux for 2 h
4. dissolutionthe starting material dissolved meanwhile
5. customAn aliquot of the reaction was partitioned between NaCO3 10% aq. (1 mL) and DCM (1 mL)
6. additionThe reaction mixture was slowly added to a mixture of water and ice
7. extractionwas extracted with DCM (250 mL)
8. extractionThe aqueous layer was further extracted with DCM (2×150 mL)
9. washthe combined organic layers were washed with water (200 mL)
10. dry with materialwith brine (200 mL) and dried over MgSO4
11. customSolvent was removed under reduced pressure
12. customThe crude product was purified
13. wash(silica gel column, eluting with Hexane/AcOEt mixtures from 100:0 to 50:50%)

ORD record

ord-6fefd7838c1a492fbbc97935bfc6f08e

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09238653B2