Methyl iodide → 6-fluoro-1-methyl-2-pyridin-3-yl-1H-indole-3-carbonitrile

HRID 1661648Notes

Reaction equation

HRID 1661648 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:17]#[N:18])=[C:7]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)[NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].IC.[C:23]([O-])(O)=O.[Na+]>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:17]#[N:18])=[C:7]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)[N:8]2[CH3:23])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 582158106-fluoro-2-pyridin-3-yl-1H-indole-3-carbonitrile

Product 1

HCID 582157086-fluoro-1-methyl-2-pyridin-3-yl-1H-indole-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A flask is charged with 6-fluoro-2-pyridin-3-yl-1H-indole-3-carbonitrile (Example 140, 50 mg, 0.21 mmol) and DMF (2 mL), and 60% sodium hydride (25 mg, 0.63 mmol) is added. The mixture is stirred at room temperature for 30 min before addition of iodomethane (45 mg, 0.315 mmol). After 1 h, saturated NaHCO3 aqueous solution (3 mL) is added to quench the reaction and the mixture is filtered and purified on Xbridge C18 eluting with a 9:1 to 1:9 water-acetonitrile gradient to give 6-fluoro-1-methyl-2-pyridin-3-yl-1H-indole-3-carbonitrile. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.77 (s, 3H), 7.19-7.26 (m, 1H), 7.66-7.76 (m, 3H), 8.14-8.19 (m, 1H), 8.80 (dd, J=4.9, 1.6 Hz, 1H), 8.89 (dd, J=2.3, 0.8 Hz, 1H). HRMS (ESI) m/z 293.1210 [(M+H+CH3CN)+ calcd for C17H14FN4: 293.1203].

Workup

  1. additionis added
  2. customto quench
  3. customthe reaction
  4. filtrationthe mixture is filtered
  5. custompurified on Xbridge
  6. washC18 eluting with a 9:1 to 1:9 water-acetonitrile gradient

Sources & evidence

ORD record
ord-175f297168954a73899d5265cd69245d
Source dataset
uspto-grants-2011_10
Patent number
US08030334B2

Reaction notes

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