Methyl iodide → HCID 178434238, compound

HRID 1484582Notes

Reaction equation

HRID 1484582 reaction equation
[F:1][CH:2]([F:26])[C:3]1[NH:4][C:5]([CH:23]([F:25])[F:24])=[C:6]([C:21]#[N:22])[CH:7]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][N:15]=[C:14]3[CH3:20])[C:8]=1[C:9]#[N:10].[C:27](=O)([O-])[O-].[Cs+].[Cs+].CI>CN(C=O)C>[F:26][CH:2]([F:1])[C:3]1[N:4]([CH3:27])[C:5]([CH:23]([F:24])[F:25])=[C:6]([C:21]#[N:22])[CH:7]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][N:15]=[C:14]3[CH3:20])[C:8]=1[C:9]#[N:10]

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 10796Cesium carbonateHCID 178434239HCID 178434239, compound

Product 1

HCID 178434238HCID 178434238, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 100 mg (0.277 mmol) 2,6-bis(difluoromethyl)-4-(3-methyl-1H-indazol-5-yl)-1,4-dihydropyridine-3,5-dicarbonitrile (Example 13) in DMF (1.5 ml) was cooled to 0° C., and 108 mg (0.33 mmol) caesium carbonate were added at this temperature. After stirring for 30 min, 21 μl (0.33 mmol) methyl iodide were added dropwise at room temperature, and the mixture was stirred at rt overnight. After this, additional methyl iodide (20 μl) was added, and stirring at rt was continued for further 48 h. The reaction mixture was then filtered, and the filtrate was directly purified by preparative RP-HPLC (acetonitrile/water+0.1% TFA isocratic 40:60 v/v) to give 12 mg (11% of th.) of the title compound.

Workup

  1. stirringthe mixture was stirred at rt overnight
  2. stirringstirring at rt
  3. waitwas continued for further 48 h
  4. filtrationThe reaction mixture was then filtered
  5. customthe filtrate was directly purified by preparative RP-HPLC (acetonitrile/water+0.1% TFA isocratic 40:60 v/v)

Sources & evidence

ORD record
ord-8a48310868ac4cb68e482b69f1058e72
Source dataset
uspto-grants-2016_08
Patent number
US09422263B2

Reaction notes

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