Methyl iodide → N-[2-(3-Cyano-5-fluorophenyl)-3-(4-methoxyphenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide

HRID 2354515Notes

Reaction equation

HRID 2354515 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:10]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=2)[CH:11]([NH:13][C:14](=[O:29])[C:15]([O:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][N:20]=2)([CH3:17])[CH3:16])[CH3:12])[CH:6]=[C:7]([F:9])[CH:8]=1)#[N:2].[C:38](=O)([O-])[O-].[Cs+].[Cs+].CI>CN(C)C=O.CCOCC>[C:1]([C:3]1[CH:4]=[C:5]([CH:10]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[CH:11]([NH:13][C:14](=[O:29])[C:15]([O:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][N:20]=2)([CH3:17])[CH3:16])[CH3:12])[CH:6]=[C:7]([F:9])[CH:8]=1)#[N:2]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 68656491N-[2-(3-cyano-5-fluorophenyl)-3-(4-hydroxyphenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide

Product 1

HCID 11375987N-[2-(3-Cyano-5-fluorophenyl)-3-(4-methoxyphenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-[2-(3-cyano-5-fluorophenyl)-3-(4-hydroxyphenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide from Example 7, Step B (14 mg, 0.028 mmol) in 1.5 mL of dimethylformamide at 0° C. was added cesium carbonate (14 mg, 0.042 mmol) and methyl iodide (5 uL, 0.084 mmol), and the reaction was allowed to warm up to room temperature over 2 h. The resulting mixture was diluted with ether (20 mL), washed with water and brine and concentrated to dryness. The residue was purified by flash column chromatography eluting with 10 to 40% ethyl acetate in hexane to give the title compound. 1H NMR (500 MHz, CD3OD): δ 8.27 (d, 1H), 7.96 (s, 1H), 7.94 (d, 1H), 7.93 (d, 1H), 7.29 (m, 1H), 7.18 (br s, 1H), 7.13 (m, 1H), 7.03 (d, 1H), 6.45 (ABq, 4H), 4.24 (m, 1H), 3.67 (s, 3H), 3.03 (dd, 1H), 2.88 (m, 1H), 2.57 (dd, 1H), 1.75 (s, 3H), 1.73 (s, 3H), 0.82 (d, 3H). LC-MS: m/e 530 (M+H)+ (3.9 min).

Workup

  1. washwashed with water and brine
  2. concentrationconcentrated to dryness
  3. customThe residue was purified by flash column chromatography
  4. washeluting with 10 to 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-b11b5996e8cf4fff8dd8e1d66f61e557
Source dataset
uspto-grants-2010_07
Patent number
US07754188B2

Reaction notes

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