Hydrochloric Acid → N-(3-Ethynyl-5-fluoro-4-methanesulfonylamino-benzyl)-3-(2-isobutoxy-6-trifluoromethyl-pyridin-3-yl)-acrylamide

HRID 2265995Notes

Reaction equation

HRID 2265995 reaction equation
Cl[C:2]1[C:7]([CH:8]=[CH:9][C:10]([NH:12][CH2:13][C:14]2[CH:19]=[C:18]([F:20])[C:17]([NH:21][S:22]([CH3:25])(=[O:24])=[O:23])=[C:16]([C:26]#[CH:27])[CH:15]=2)=[O:11])=[CH:6][CH:5]=[C:4]([C:28]([F:31])([F:30])[F:29])[N:3]=1.[CH3:32][CH:33]([CH3:36])[CH2:34][OH:35].[H-].[Na+].Cl>CN(C=O)C.O>[C:26]([C:16]1[CH:15]=[C:14]([CH:19]=[C:18]([F:20])[C:17]=1[NH:21][S:22]([CH3:25])(=[O:24])=[O:23])[CH2:13][NH:12][C:10](=[O:11])[CH:9]=[CH:8][C:7]1[C:2]([O:35][CH2:34][CH:33]([CH3:36])[CH3:32])=[N:3][C:4]([C:28]([F:31])([F:30])[F:29])=[CH:5][CH:6]=1)#[CH:27]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6560IsobutanolHCID 24758Sodium hydrideHCID 743823853-(2-Chloro-6-trifluoromethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluoro-4-methanesulfonylamino-benzyl)-acrylamide

Product 1

HCID 74382684N-(3-Ethynyl-5-fluoro-4-methanesulfonylamino-benzyl)-3-(2-isobutoxy-6-trifluoromethyl-pyridin-3-yl)-acrylamideYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-(2-chloro-6-trifluoromethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluoro-4-methanesulfonylamino-benzyl)-acrylamide (50 mg, 0.11 mmol), 2-methyl-1-propanol (20 μl, 0.22 mmol) and 60% NaH (13 mg, 0.33 mmol) in DMF was stirred at ambient temperature for 4 hrs. The reaction mixture was diluted with water and then acidified with 2N HCl solution. The aqueous phase was extracted with EtOAc and the combined organic phase was washed with brine, dried over anhydrous MgSO4 and concentrated under reduced pressure. The resulting residue was purified by column chromatography (Hex EtOAc=1/2) to give the title compound (12 mg, 40%).

Workup

  1. extractionThe aqueous phase was extracted with EtOAc
  2. washthe combined organic phase was washed with brine
  3. dry with materialdried over anhydrous MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by column chromatography (Hex EtOAc=1/2)

Sources & evidence

ORD record
ord-d7248fecf35d402481ec7a69ce8521b6
Source dataset
uspto-grants-2010_12
Patent number
US07858621B2

Reaction notes

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