Acetic Acid → 7-[2-(tert-butyldimethylsilanyloxy)ethylamino]-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

HRID 1162936Notes

Reaction equation

HRID 1162936 reaction equation
[Si:1]([O:8][CH2:9][CH:10]=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(O)(=O)C.[NH2:16][C:17]1[CH:26]=[C:25]2[C:20]([CH:21]=[C:22]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:34]([F:37])([F:36])[F:35])[NH:23][C:24]2=[O:27])=[CH:19][CH:18]=1.B(C#N)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.CO>[Si:1]([O:8][CH2:9][CH2:10][NH:16][C:17]1[CH:26]=[C:25]2[C:20]([CH:21]=[C:22]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:34]([F:37])([F:35])[F:36])[NH:23][C:24]2=[O:27])=[CH:19][CH:18]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehydeHCID 231567387-amino-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-oneHCID 86626745Sodium cyanoborate

Product 1

HCID 575581107-[2-(tert-butyldimethylsilanyloxy)ethylamino]-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-oneYield 92.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(tert-Butyldimethylsilanyloxy)acetaldehyde (93.9 μL, 0.493 mmol) and acetic acid (169 μL, 2.96 mmol) were added to a methanol solution (30 ml) that contained the 7-amino-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (150 mg, 0.493 mmol) prepared in step C of Example 1-1. The obtained solution was cooled to 0° C., and sodium cyanoborate (1M THF solution, 1.48 mL, 1.48 mmol) was then added thereto. The obtained mixture was stirred at a room temperature for 18 hours. The reaction solution was poured into a mixed solution of ethyl acetate and a saturated sodium bicarbonate aqueous solution. An organic layer was dried over anhydrous sodium sulfate, and the solvent was then distilled away under reduced pressure. The obtained residue was purified by silica gel column chromatography (methylene chloride:methanol=40:1), so as to obtain 7-[2-(tert-butyldimethylsilanyloxy)ethylamino]-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (210 mg, 92%).

Workup

  1. dry with materialAn organic layer was dried over anhydrous sodium sulfate
  2. distillationthe solvent was then distilled away under reduced pressure
  3. customThe obtained residue was purified by silica gel column chromatography (methylene chloride:methanol=40:1)

Sources & evidence

ORD record
ord-9728c65e11cd4b5c853d478a1b715006
Source dataset
uspto-grants-2010_10
Patent number
US07820693B2

Reaction notes

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