Methyl iodide → HCID 59639514, compound

HRID 2357268Notes

Reaction equation

HRID 2357268 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[CH3:26])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:32].[H-].[Na+].I[CH3:36].[NH4+].[Cl-]>CN(C=O)C>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16]([N:27]([CH3:36])[S:28]([CH3:31])(=[O:30])=[O:29])[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[CH3:26])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:32]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 59639619HCID 59639619, compound

Product 1

HCID 59639514HCID 59639514, compoundYield 84.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the solution of N-[8-(2,6-difluoro-phenyl)-4-(4-fluoro-2-methyl-phenyl)-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-yl]-methanesulfonamide (92 mg, 0.2 mmol) in anhydrous DMF (2 mL) was added NaH (80 mg of 60% dispersion in mineral oil, 2 mmol, 10 eq) and the reaction mixture was stirred for 30 minutes at 23°. Iodomethane (280 mg, 2 mmol, 10 eq) was added and the reaction mixture was stirred 1 h at 23°. Saturated aq NH4Cl (5 mL) was added and the reaction mixture was extracted with EtOAc (2×20 mL). Organic layers were combined, washed with satd aq NaCl, dried (MgSO4), filtered and solvent was evaporated. The yellow residue was then purified by Flash chromatography to give 80 mg of pure N-[8-(2,6-difluoro-phenyl)-4-(4-fluoro-2-methyl-phenyl)-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-yl]-N-methyl-methanesulfonamide. 1H-NMR (CDCl3): δ 2.22 (s, 3H), 2.96 (s, 3H), 3.30 (s, 3H), 6.68 (d, 1H, J=9.8 Hz), 7.02 (m, 4H), 7.213 (m, 1H), 7.42 (m, 2H), LC MS (m/e)=475.4 (MH+). Rt=2.25 min.

Workup

  1. stirringthe reaction mixture was stirred 1 h at 23°
  2. extractionthe reaction mixture was extracted with EtOAc (2×20 mL)
  3. washwashed with satd aq NaCl
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customsolvent was evaporated
  7. customThe yellow residue was then purified by Flash chromatography

Sources & evidence

ORD record
ord-5b5aef76f04743ba96581a1338e0deed
Source dataset
uspto-grants-2010_07
Patent number
US07759486B2

Reaction notes

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