Methyl iodide → HCID 178493284, compound

HRID 81245Notes

Reaction equation

HRID 81245 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[C:11]([OH:34])=[C:10]([C:35]#[N:36])[N:9]=2)[CH:5]=[N:6][CH:7]=1.[C:37]([O-])([O-])=O.[Cs+].[Cs+].CI>CN(C=O)C.CCOC(C)=O>[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[C:11]([O:34][CH3:37])=[C:10]([C:35]#[N:36])[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 178461243HCID 178461243, compound

Product 1

HCID 178493284HCID 178493284, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-7-hydroxy-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (24.5 mg, 0.048 mmol) in DMF (2 mL) were added Cs2CO3 (31.5 mg, 0.097 mmol) and MeI (6 μL, 0.097 mmol). The reaction was stirred at room temperature for 15 minutes and then diluted with EtOAc (40 mL) and washed with water (10 mL) and brine (10 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified on a silica gel column with 0 to 100% EtOAc/hexanes to afford 4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-7-methoxy-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd for C28H33ClN6O2 [M+H]+=521. found=521.

Workup

  1. washwashed with water (10 mL) and brine (10 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified on a silica gel column with 0 to 100% EtOAc/hexanes

Sources & evidence

ORD record
ord-309c51d59f7c4d5c802fae6ae324e412
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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