Hexachloroethane → [1-(6-Fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1-methyl-ethyl]-dimethyl-amine

To a solution of Intermediate 76a (195 mg, 0.81 mmol), Ph3P (426 mg, 1.62 mmol) and Et3N (452 □L, 3.25 mmol) in THF (9.00 mL) at 0° C. was added hexachloroethane (385 mg, 1.62 mmol). The reaction was stirred at RT overnight then partitioned between EtOAc and water. The aqueous layer was then extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was dissolved in MeOH and loaded onto an SCX-2 cartridge, which was washed with MeOH and eluted with 2M NH3 in MeOH. The reaction showed 50% conversion so was re-submitted to the reaction conditions overnight at 50° C. The workup and purification procedures were repeated to give the title compound (153 mg, 85%). 1H NMR (300 MHz, CDCl3): 1.60 (6H, s), 2.20 (6H, s), 7.16 (1H, ddd, J 9.9, 7.4, 2.4), 7.71 (1H, ddd, J 9.9, 5.0, 0.8), 8.89 (1H, ddd, J 4.4, 2.4, 0.8).

1. customthen partitioned between EtOAc and water
2. extractionThe aqueous layer was then extracted with EtOAc (3×)
3. washThe combined organic layers were washed with brine
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. customevaporated in vacuo
7. dissolutionThe residue was dissolved in MeOH
8. washwas washed with MeOH
9. washeluted with 2M NH3 in MeOH
10. customso was re-submitted to the reaction conditions overnight at 50° C
11. customThe workup and purification procedures

ORD record

ord-f09c7dd3527d4bccba0db7da2e45256b

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139584B2