Iodoethane → 2-(3,5-Bis-trifluoromethyl-phenyl)-N-[6-[3-(ethyl-methanesulfonyl-amino)-pyrrolidin-1-yl]-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramide

HRID 547767Notes

Reaction equation

HRID 547767 reaction equation
[F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([C:13]([CH3:43])([CH3:42])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:32]3[CH2:36][CH2:35][C@H:34]([NH:37][S:38]([CH3:41])(=[O:40])=[O:39])[CH2:33]3)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[H-].[Na+].I[CH2:49][CH3:50].COC(C)(C)C>CN(C)C=O>[F:11][C:9]([F:10])([F:12])[C:7]1[CH:6]=[C:5]([C:13]([CH3:43])([CH3:42])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:32]3[CH2:36][CH2:35][CH:34]([N:37]([CH2:49][CH3:50])[S:38]([CH3:41])(=[O:40])=[O:39])[CH2:33]3)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:4]=[C:3]([C:2]([F:1])([F:44])[F:45])[CH:8]=1

Participants

6

Reactant 4

HCID 6340IodoethaneHCID 15413tert-Butyl methyl etherHCID 24758Sodium hydrideHCID 86597675(S)-2-(3,5-Bis-trifluoromethyl-phenyl)-N-[4-(4-fluoro-2-methyl-phenyl)-6-(3-methanesulfonylamino-pyrrolidin-1-yl)-pyridin-3-yl]-N-methyl-isobutyramide

Product 1

HCID 111932822-(3,5-Bis-trifluoromethyl-phenyl)-N-[6-[3-(ethyl-methanesulfonyl-amino)-pyrrolidin-1-yl]-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramideYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 150 mg (0.227 mmol) (S)-2-(3,5-bis-trifluoromethyl-phenyl)-N-[4-(4-fluoro-2-methyl-phenyl)-6-(3-methanesulfonylamino-pyrrolidin-1-yl)-pyridin-3-yl]-N-methyl-isobutyramide in 1 ml dimethylformamide were added 14 mg (0.35 mmol) sodium hydride (60% dispersion in mineral oil). After stirring at room temperature for 30 min. 22 mg (0.27 mmol) iodoethane were added. The reaction mixture was stirred at room temperature for 18 h, followed by dilution with 10 ml tert-butyl methyl ether and washing with 20 ml water and with 10 ml of a saturated aqueous solution of sodium carbonate. The combined organic layers were dried over sodium sulfate, concentrated and purified by flash chromatography to give 86 mg (55%) of the title compound as an off-white foam.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 18 h
  2. washwashing with 20 ml water and with 10 ml of a saturated aqueous solution of sodium carbonate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated
  5. custompurified by flash chromatography

Sources & evidence

ORD record
ord-ac1eb397eb4d4f51b32007661e634edf
Source dataset
uspto-grants-2011_05
Patent number
US07939533B2

Reaction notes

Loading…