Methyl iodide → 2-(2-chloro-5-fluorophenyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]propanamide

HRID 1487343Notes

Reaction equation

HRID 1487343 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1[CH2:11][C:12]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=2[F:29])=[C:17]([C:30]2[C:35]([O:36][CH2:37][CH3:38])=[CH:34][C:33](=[O:39])[N:32]([CH3:40])[CH:31]=2)[CH:16]=1)=[O:13].I[CH3:42]>CN(C=O)C>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1[CH:11]([CH3:42])[C:12]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=2[F:29])=[C:17]([C:30]2[C:35]([O:36][CH2:37][CH3:38])=[CH:34][C:33](=[O:39])[N:32]([CH3:40])[CH:31]=2)[CH:16]=1)=[O:13]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 118116343HCID 118116343, compound

Product 1

HCID 1181166262-(2-chloro-5-fluorophenyl)-N-[4-(2,4-difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]propanamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A 4 mL vial with stirbar was charged with sodium hydride, dry 95% (2.9 mg, 0.115 mmol), placed in an ice bath and charged with a solution of Example 1H (0.0527 g, 0.097 mmol) in DMF (1 mL). After stirring 10 min at 0° C., iodomethane (8 μL, 0.128 mmol) was added by syringe. After 1 hour, the mixture was partitioned between 25 mL each of ethyl acetate and aqueous ammonium chloride. The organics were dried over anhydrous sodium sulfate. After filtration and solvent removal, the material was purified by reverse phase HPLC (C18, CH3CN/water (0.1% TFA), 0-100%) to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ 10.26 (s, 1H), 7.60 (d, J=2.6 Hz, 1H), 7.58 (s, 1H), 7.54-7.49 (m, 2H), 7.46-7.25 (m, 2H), 7.22-6.92 (m, 3H), 6.87 (d, J=8.8 Hz, 1H), 5.79 (s, 1H), 4.15 (q, J=7.1 Hz, 1H), 3.93 (d, J=7.0 Hz, 2H), 3.34 (s, 3H), 1.47 (d, J=7.1 Hz, 3H), 1.14 (t, J=6.9 Hz, 3H). MS (ESI) 557.1 (M+H)+.

Workup

  1. customdry 95% (2.9 mg, 0.115 mmol)
  2. customplaced in an ice bath
  3. waitAfter 1 hour
  4. customthe mixture was partitioned between 25 mL each of ethyl acetate and aqueous ammonium chloride
  5. dry with materialThe organics were dried over anhydrous sodium sulfate
  6. filtrationAfter filtration and solvent removal
  7. customthe material was purified by reverse phase HPLC (C18, CH3CN/water (0.1% TFA), 0-100%)

Sources & evidence

ORD record
ord-df8d42a502504084af5ef1b500c42cfb
Source dataset
uspto-grants-2016_08
Patent number
US09428514B2

Reaction notes

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