Cesium carbonate → N-{2-(3-cyano-5-fluorophenyl)-3-[4-(2-fluoroethoxy)phenyl]-1-methylpropyl}-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide

HRID 2354516Notes

Reaction equation

HRID 2354516 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(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:49][CH2:50][F:51])(=O)=O>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][CH2:49][CH2:50][F:51])=[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 10796Cesium carbonateHCID 680342-Fluoroethyl methanesulfonateHCID 68656491N-[2-(3-cyano-5-fluorophenyl)-3-(4-hydroxyphenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide

Product 1

HCID 11478538N-{2-(3-cyano-5-fluorophenyl)-3-[4-(2-fluoroethoxy)phenyl]-1-methylpropyl}-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

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 (15 mg, 0.039 mmol) in 2 mL of dimethylformamide was added cesium carbonate (15 mg, 0.046 mmol) and 2-fluoroethyl methanesulfonate (20 uL, 0.16 mmol), and the reaction was stirred at 70° C. for 0.5 h. The resulting mixture was diluted with ether (20 mL), washed with water and brine and concentrated to dryness, and the residue was purified by flash column chromatography on silica gel eluted with 10 to 40% ethyl acetate in hexane to give N-{2-(3-cyano-5-fluorophenyl)-3-[4-(2-fluoroethoxy)phenyl]-1-methylpropyl}-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide. 1H NMR (500 MHz, CD3OD): PL 87 δ 8.27 (br s, 1H), 7.94 (dd, 1H), 7.48 (d, 1H), 7.73-7.32 (m, 3H), 7.04 (s, 1H), 6.64 (s, 4H) 4.68 (m, 1H), 4.59 (m, 1H), 4.25 (m, 1H), 4.11 (m, 1H), 4.04 (m, 1H), 3.02 (dd, 1H), 2.84 (m, 1H), 2.57 (dd, 1H), 1.75 (s, 3H), 1.73 (s, 3H), 0.80 (d, 3H). LC-MS: m/e 544 (M+H)+ (3.8 min).

Workup

  1. washwashed with water and brine
  2. concentrationconcentrated to dryness
  3. customthe residue was purified by flash column chromatography on silica gel
  4. washeluted with 10 to 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-b0918568d17642aaa4414147a6bed5f8
Source dataset
uspto-grants-2010_07
Patent number
US07754188B2

Reaction notes

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