2-(Benzenesulfonyl)-3-phenyloxaziridine → Methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

Temperature

-78 °C

To a stirred solution of 0.9M KHMDS/THF (9.76 mL, 8.79 mmol) in THF (25 mL) at −78° C. was added dropwise a THF (25 mL) solution of methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate (2.5 g, 6.76 mmol) over 5 min. After 30 min, a THF (20 mL) solution of 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (2.296 g, 8.79 mmol) was added to the resulting red reaction mixture and stirred for additional 30 min at −78° C. Then, the resulting orange reaction mixture was quenched with sat. NH4Cl (50 mL), diluted with EtOAc (200 mL), washed with water (100 mL), brine (100 mL), dried (Na2SO4), filtered and concentrated to give yellow solid. This was purified by flash column chromatography on silica gel column (5-40% EtOAc/hexane) to afford the 2.2 g desired methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate as off-white solid. Impurities were present by NMR and LCMS. Used in the next step without further purification. 1H NMR (500 MHz, CDCl3) δ 7.77-7.71 (m, 2H), 7.19 (d, J=7.6 Hz, 1H), 6.93 (s, 1H), 5.78 (d, J=2.7 Hz, 1H), 3.86 (s, 3H), 3.56 (d, J=2.7 Hz, 1H), 2.89-1.81 (m, 4H), 2.64 (s, 3H), 1.86 (dt, J=6.5, 3.3 Hz, 4H). LCMS (M+H)=386.3.

1. customThen, the resulting orange reaction mixture was quenched with sat. NH4Cl (50 mL)
2. additiondiluted with EtOAc (200 mL)
3. washwashed with water (100 mL), brine (100 mL)
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customto give yellow solid
8. customThis was purified by flash column chromatography on silica gel column (5-40% EtOAc/hexane)

ORD record

ord-9ead97f027a949698373fb9ab3936f6f

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09034882B2