Hexachloroethane → HCID 178461239, compound

HRID 81242Notes

Reaction equation

HRID 81242 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:26][C@H:27]4[CH2:32][CH2:31][C@H:30]([CH3:33])[CH2:29][CH2:28]4)[C:15]([N:17]4[CH2:22][CH2:21][O:20][C@@H:19]5[CH2:23][CH2:24][CH2:25][C@@H:18]45)=[N:16][C:12]=3[CH:11]=[C:10]([C:34]#[N:35])[N:9]=2)[CH:5]=[N:6][CH:7]=1.[Cl-].[Li+].CC1(C)CCCC(C)(C)N1[Mg][Cl:48].ClC(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1>[Cl:48][C:11]1[C:12]2[N:16]=[C:15]([N:17]3[CH2:22][CH2:21][O:20][C@@H:19]4[CH2:23][CH2:24][CH2:25][C@@H:18]34)[N:14]([CH2:26][C@H:27]3[CH2:32][CH2:31][C@H:30]([CH3:33])[CH2:29][CH2:28]3)[C:13]=2[C:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)=[N:9][C:10]=1[C:34]#[N:35]

Participants

5

Reactant 3

HCID 6214HexachloroethaneHCID 178424953HCID 178424953, compoundHCID 178461236HCID 178461236, compound

Product 1

HCID 178461239HCID 178461239, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-e8fcdb4da8e9459e8aaa7f2709df0a60
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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