Triethylamine → HCID 90067522, compound

Triethylamine (30 μl, 0.215 mmol) and methanesulfonyl chloride (4.5 μl, 0.058 mmol) were added to a stirred suspension of (3R,3aR,6R,6aR)-6-[[6-chloro-5-[4-(5,6-dihydro-4H-pyrrolo[3,4-c]pyrazol-2-yl)phenyl]-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol; 2,2,2-trifluoroacetate (29.1 mg, 0.049 mmol) in DCM (0.5 ml). After 10 min, 1,4-dioxane (0.5 ml) was added to the reaction mixture. Following sonication, the reaction mixture was a yellow suspension. After stirring for an additional 10 min, the reaction mixture was evaporated under reduced pressure. DMF (0.5 ml), triethylamine (30 μl, 0.215 mmol), and methanesulfonyl chloride (4.5 μl, 0.058 mmol) were added to the resulting residue to give a fine yellow suspension that was stirred at room temperature. After 30 min, EtOAc (2 ml) was added to the reaction mixture, causing a white precipitate to form. The reaction mixture was filtered and the filtrate was partitioned between EtOAc (30 ml) and water (30 ml). The organic filtrate was washed with water (2×10 ml) and brine (1×10 ml), dried over MgSO4, filtered, and evaporated under reduced pressure to give a white residue. THF (1.0 ml) was added followed by potassium trimethylsilanolate (41.6 mg, 0.324 mmol). The reaction mixture was a pale yellow suspension that was stirred at room temperature. After 20 hours, the reaction mixture was evaporated under reduced pressure to give a yellow/white solid. This material was purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-80% acetonitrile/water+0.05% TFA gradient followed by a 80% acetonitrile/water+0.05% TFA flush. The product fractions were combined, evaporated under reduced pressure, and lyophilized from ethanol and benzene to give the title compound as a white solid. LC-MS: calculated for C24H23ClN6O6S 558.11 observed m/e: 559.18 (M+H)+ (Rt 1.06/2 min); 1H NMR δ (ppm) ((CD3)2SO): 8.43 (s, 1H), 7.98 (broad s, 1H), 7.90 (d, J=8.5 Hz, 2H), 7.77 (d, J=8.6 Hz, 1H), 5.48 (qt, J=5.7 Hz, 1H), 4.99 (d, J=6.5 Hz, 1H), 4.84 (t, J=5.1 Hz, 1H), 4.54 (s, 2H), 4.51 (s, 2H), 4.36 (t, J=4.8 Hz, 1H), 4.10-4.17 (m, 2H), 3.91 (dd, J=5.9 Hz, J=9.5 Hz, 1H), 3.78 (t, J=7.4 Hz, 1H), 3.43 (t, J=8.5 Hz, 1H), 3.05 (s, 3H).

1. customsonication
2. customthe reaction mixture was evaporated under reduced pressure
3. customto give a fine yellow suspension that
4. stirringwas stirred at room temperature
5. waitAfter 30 min
6. customto form
7. filtrationThe reaction mixture was filtered
8. customthe filtrate was partitioned between EtOAc (30 ml) and water (30 ml)
9. washThe organic filtrate was washed with water (2×10 ml) and brine (1×10 ml)
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. customevaporated under reduced pressure
13. customto give a white residue
14. stirringwas stirred at room temperature
15. waitAfter 20 hours
16. customthe reaction mixture was evaporated under reduced pressure
17. customto give a yellow/white solid
18. customThis material was purified by preparative HPLC reverse phase (C-18)
19. washeluting with a 20%-80% acetonitrile/water+0.05% TFA
20. customflush
21. customevaporated under reduced pressure

ORD record

ord-2da62818dcff4f9c9e9276211a1dc0d9

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09290517B2