Methyl iodide → HCID 70817367, compound

HRID 82132Notes

Reaction equation

HRID 82132 reaction equation
[C:1]([N:5]1[C:9]2[N:10]=[CH:11][N:12]=[CH:13][C:8]=2[C:7]([C:14]([C:16]2[CH:17]=[C:18]([NH:22][C:23](=[O:32])[CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[CH:19]=[N:20][CH:21]=2)=[O:15])=[CH:6]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:35]I.[Cl-].[NH4+]>C1COCC1>[C:1]([N:5]1[C:9]2[N:10]=[CH:11][N:12]=[CH:13][C:8]=2[C:7]([C:14]([C:16]2[CH:17]=[C:18]([N:22]([CH3:35])[C:23](=[O:32])[CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[CH:19]=[N:20][CH:21]=2)=[O:15])=[CH:6]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 70817722HCID 70817722, compound

Product 1

HCID 70817367HCID 70817367, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of N-[5-(7-tert-Butyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-pyridin-3-yl]-2-(4-fluoro-phenyl)-acetamide (Example 546, 115 mg, 0.27 mmol) in anhydrous THF (4.5 mL), was added NaH (60% in paraffin oil, 10.7 mg, 0.27 mmol) at 0° C. under nitrogen and the resulting mixture stirred for 10 min. MeI (0.017 mL, 0.27 mmol) was then added and the reaction mixture was stirred at room temperature for 1 hour. Aqueous saturated ammonium chloride (5 mL) was added and the mixture extracted with ethyl acetate (2×10 mL). The organic phase was washed with water (10 mL), brine (10 mL), dried over sodium sulphate and evaporated to dryness in vacuo. The crude material was purified via preparative TLC (eluting with 5% methanol in DCM) to afford the title compound as off white solid in 46% yield, 55 mg. 1H NMR (400 MHz, DMSO-D6) δ: 1.79 (s, 9H), 3.28 (s, 3H), 3.58 (br, 2H), 7.08-7.20 (m, 4H), 8.20 (s, 1H), 8.32 (s, 1H), 8.83 (s, 1H), 8.97 (br, 1H), 9.01 (s, 1H), 9.50 (s, 1H); LCMS (system 10): Rt=3.08 min; m/z 446 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 1 hour
  2. extractionthe mixture extracted with ethyl acetate (2×10 mL)
  3. washThe organic phase was washed with water (10 mL), brine (10 mL)
  4. dry with materialdried over sodium sulphate
  5. customevaporated to dryness in vacuo
  6. customThe crude material was purified via preparative TLC (eluting with 5% methanol in DCM)

Sources & evidence

ORD record
ord-e8757913f3ff43d79f3119adfcc9feaf
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Reaction notes

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