Hexachloroethane → HCID 178461239, Verbindung

To a −78° C. solution of 4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Example 3.2, Step 3; 250 mg, 0.509 mmol) in THF (7 mL) was added 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex (Aldrich, 1M in THF/toluene) (1.02 mL, 1.02 mmol). The resulting solution was stirred at −78° C. for 45 minutes, and then hexachloroethane (301 mg, 1.273 mmol) was added as a solid in one portion. The reaction was allowed to warm slowly to 10° C. over 2 hours and then quenched with saturated NH4Cl (10 mL). EtOAc (75 ml) was added, and the organic layer was washed with water and brine (25 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue on a silica gel column eluting with 0 to 50% EtOAc/DCM afforded 7-chloro-4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd for C27H30Cl2N6O [M+H]+=525. found=525.

1. temperatureto warm slowly to 10° C. over 2 hours
2. customquenched with saturated NH4Cl (10 mL)
3. additionEtOAc (75 ml) was added
4. washthe organic layer was washed with water and brine (25 mL each)
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customPurification of the residue on a silica gel column
9. washeluting with 0 to 50% EtOAc/DCM

ORD-Eintrag

ord-536d9718303b4d4ab8f9e91dba755518

Quelldatensatz

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08962611B2