Sodium Hydroxide → HCID 86625532, compound

HRID 2266017Notes

Reaction equation

HRID 2266017 reaction equation
C([O:3][C:4](=[O:23])[CH:5]=[CH:6][C:7]1[C:8]([C:17]#[C:18][Si](C)(C)C)=[N:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][CH:12]=1)C.[OH-].[Na+]>C1COCC1.CO.O>[C:17]([C:8]1[C:7]([CH:6]=[CH:5][C:4]([OH:23])=[O:3])=[CH:12][CH:11]=[C:10]([C:13]([F:16])([F:14])[F:15])[N:9]=1)#[CH:18]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 68785384HCID 68785384, compound

Product 1

HCID 86625532HCID 86625532, compoundYield 117.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 3-(6-trifluoromethyl-2-trimethylsilanylethynyl-pyridin-3-yl)-acrylic acid ethyl ester (68 mg, 0.169 mmol) in THF (1 ml) and CH3OH (0.5 ml) was added a solution of 1N-NaOH (0.5 ml) and the mixture was stirred for 50 min at room temperature. The resulting residue was dissolved in H2O and then washed three times with EtOAc, acidified with 1N HCl to pH 1˜2. The solution was extracted three times with methylene chloride and then dried over anhyd. Na2SO4 and concentrated in vacuo to give 3-(2-ethynyl-6-trifluoromethyl-pyridin-3-yl)-acrylic acid (48 mg, 99%). To a suspension of N-(4-aminomethyl-2-ethynyl-6-fluoro-phenyl)-methanesulfonamide, HCl salt (83 mg, 0.298 mmol) in THF (3 mL) was added N-methylmorpholine (0.066 ml, 0.597 mmol). The mixture was stirred for 5 minutes, to which were added 3-(2-ethynyl-6-trifluoromethyl-pyridin-3-yl)-acrylic acid (48 mg, 0.065 mmol) and 4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMTMM, 71.4 mg, 0.258 mmol). The mixture was stirred overnight at room temperature and was concentrated under reduced pressure. The residue was diluted with EtOAc and water. The organic layer was washed with saturated sodium bicarbonate, 1N HCl and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by recrystallization from CH2Cl2 to give N-(3-ethynyl-5-fluoro-4-methanesulfonylamino-benzyl)-3-(2-ethynyl-6-trifluoromethyl-pyridin-3-yl)-acrylamide (30 mg, 32%).

Workup

  1. washwashed three times with EtOAc
  2. extractionThe solution was extracted three times with methylene chloride
  3. customdried over anhyd
  4. concentrationNa2SO4 and concentrated in vacuo

Sources & evidence

ORD record
ord-e87083969d2b480bb9e687ec1cdad634
Source dataset
uspto-grants-2010_12
Patent number
US07858621B2

Reaction notes

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