Water → HCID 178428413, compound

HRID 408556Notes

Reaction equation

HRID 408556 reaction equation
[CH3:1][C:2]1[NH:7][C:6]2[CH2:8][O:9][C:10](=[O:11])[C:5]=2[CH:4]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][N:16]=[C:15]3[CH3:21])[C:3]=1[C:22]#[N:23].[C:24](=O)([O-])[O-].[Cs+].[Cs+].CI.O>CN(C=O)C>[CH3:24][N:7]1[C:2]([CH3:1])=[C:3]([C:22]#[N:23])[CH:4]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][N:16]=[C:15]3[CH3:21])[C:5]2[C:10](=[O:11])[O:9][CH2:8][C:6]1=2

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodide3×HCID 10796Cesium carbonate2×HCID 178428412HCID 178428412, compound

Product 1

HCID 178428413HCID 178428413, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 100 mg (0.326 mmol) 2-methyl-4-(3-methyl-1H-indazol-5-yl)-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridine-3-carbonitrile (Example 1) in DMF (2 ml) was cooled to 0° C. 128 mg (0.392 mmol) caesium carbonate were added at this temperature, and after 30 min 14 μl (0.229 mmol) methyl iodide were added dropwise. After stirring overnight at rt, additional methyl iodide (2 μl) was added, and stirring at rt was continued for further 3 h. Again, methyl iodide (6 μl) and a small amount of caesium carbonate were added, and the reaction mixture was stirred at rt overnight before water (1 ml) was added. The solution was directly purified first by preparative RP-HPLC (acetonitrile/water+0.1% TFA gradient) followed by preparative TLC (eluent: dichloromethane/ethanol 20:1) to give 11 mg (11% of th.) of the title compound.

Workup

  1. stirringstirring at rt
  2. waitwas continued for further 3 h
  3. additionwas added
  4. customThe solution was directly purified first by preparative RP-HPLC (acetonitrile/water+0.1% TFA gradient)

Sources & evidence

ORD record
ord-5ab087b0a70b420d87340f8179d03c8d
Source dataset
uspto-grants-2014_06
Patent number
US08759341B2

Reaction notes

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