Methyl iodide → HCID 67209535, compound

HRID 402495Notes

Reaction equation

HRID 402495 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[C:8]([CH:10]([NH:12][C:13](=[O:30])[CH2:14][O:15][C:16]3[N:21]=[C:20]4[N:22]([CH3:28])[N:23]=[C:24]([CH:25]5[CH2:27][CH2:26]5)[C:19]4=[C:18]([CH3:29])[CH:17]=3)[CH3:11])[CH:9]=[C:4]2[CH:3]=[CH:2]1.[CH3:31]I.[H-].[Na+]>CN(C=O)C.CCOC(C)=O.O>[CH:25]1([C:24]2[C:19]3[C:20](=[N:21][C:16]([O:15][CH2:14][C:13]([NH:12][CH:10]([C:8]4[CH:9]=[C:4]5[CH:3]=[CH:2][N:1]([CH3:31])[C:5]5=[N:6][CH:7]=4)[CH3:11])=[O:30])=[CH:17][C:18]=3[CH3:29])[N:22]([CH3:28])[N:23]=2)[CH2:27][CH2:26]1

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67209282HCID 67209282, compound

Product 1

HCID 67209535HCID 67209535, compoundYield 58%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-(1-(1H-pyrrolo[2,3-b]pyridin-5-yl)ethyl)-2-(3-cyclopropyl-1,4-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yloxy)acetamide (example 6.57, 25 mg, 0.062 mmol) was dissolved in DMF (1 ml) and methyliodide (4.25 μl, 0.068 mmol) was added, followed by NaH (60% in mineral oil, 2.7 mg, 0.068 mmol). After stirring for 1 h at rt the reaction was diluted with EtOAc (1 ml) and water (2 ml) and extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate, and the solvents were evaporated under reduced pressure. The crude product was purified on preparative TLC (DCM/MeOH 95/5) to give the product as colorless solid (15 mg, 58%). [1H-NMR (DMSO-d6, 600 MHz) δ 8.58 (d, 1H), 8.23 (s, 1H), 7.83 (s, 1H), 7.48 (d, 1H), 6.47 (s, 1H, 6.30 (d, 1H, 5.13-5.09 (m, 1H), 4.81 (d, 1H), 4.76 (d, 1H), 3.78 (s, 3H), 3.63 (s, 3H), 2.65 (s, 3H), 2.27-2.22 (m, 1H), 3.06 (d, 3H), 0.93-0.84 (m, 4H); LCMS RtL=2.901 min; [M+H]+=419.2]

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. customthe solvents were evaporated under reduced pressure
  5. customThe crude product was purified on preparative TLC (DCM/MeOH 95/5)

Sources & evidence

ORD record
ord-159de69d7c974069bdc25d151206aaa3
Source dataset
uspto-grants-2014_06
Patent number
US08742106B2

Reaction notes

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