Methyl iodide → HCID 86664686, compound

HRID 1484749Notes

Reaction equation

HRID 1484749 reaction equation
[CH2:1]([N:3]([C:17]1[C:18]([CH3:28])=[N:19][N:20]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)[CH:21]=1)[C:4](=[O:16])[CH2:5][C:6]([OH:15])([C:11]([F:14])([F:13])[F:12])[C:7]([F:10])([F:9])[F:8])[CH3:2].[H-].[Na+].IC.[CH3:33]COC(C)=O.CCCCCC>CN(C=O)C.O>[CH2:1]([N:3]([C:17]1[C:18]([CH3:28])=[N:19][N:20]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)[CH:21]=1)[C:4](=[O:16])[CH2:5][C:6]([O:15][CH3:33])([C:7]([F:9])([F:8])[F:10])[C:11]([F:14])([F:12])[F:13])[CH3:2]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 21226206Ethyl acetate hexaneHCID 86664687HCID 86664687, compound

Product 1

HCID 86664686HCID 86664686, compoundYield 27.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-ethyl-4,4,4-trifluoro-3-hydroxy-N-(3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-(trifluoromethyl)butanamide (184 mg, 0.448 mmol) in DMF (3 mL) stirring at 0° C. was added sodium hydride (26.9 mg, 0.673 mmol). The solution was stirred at 0° C. for 0.5 hour. Then iodomethane (0.034 mL, 0.538 mmol) was added and ice bath was removed and the mixture was stirred at 25° C. overnight. Reaction was worked up by slow addition of water and further diluted with 20 mL of water, then extracted with 4×20 mL of EtOAc. The combined organic layers were washed with water, dried over Na2SO4 and concentrated. Silica Gel chromatography (0-100% EtOAc/hexane) gave N-ethyl-4,4,4-trifluoro-3-methoxy-N-(3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-(trifluoromethyl)butanamide (52 mg, 0.123 mmol, 27.3% yield) as a white solid: mp=83-86° C.; 1H NMR (400 MHz, CDCl3) δ 8.94 (d, J=2.5 Hz, 1H), 8.59 (dd, J=4.7, 1.3 Hz, 1H), 8.01 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.85 (s, 1H), 7.44 (ddd, J=8.3, 4.8, 0.6 Hz, 1H), 4.00 (brs, 1H), 3.73 (s, 3H), 3.39 (brs, 1H), 2.86 (s, 2H), 2.26 (s, 3H), 1.16 (t, J=7.1 Hz, 3H); ESIMS m/z 425 ([M+H]+); IR (Thin film) 1664 cm−1.

Workup

  1. customice bath was removed
  2. stirringthe mixture was stirred at 25° C. overnight
  3. customReaction
  4. extractionextracted with 4×20 mL of EtOAc
  5. washThe combined organic layers were washed with water
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-925713ae071447bda2890d3826bcfca6
Source dataset
uspto-grants-2016_08
Patent number
US09422278B2

Reaction notes

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