Glycolaldehyde dimer → 7-(2-hydroxyethylamino)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

HRID 1098293Notes

Reaction equation

HRID 1098293 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]([F:22])([F:21])[F:20])[NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1.[CH2:23]1OC(O)C[O:25][CH:24]1O.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO.C(O)(=O)C>[OH:25][CH2:24][CH2:23][NH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]([F:22])([F:20])[F:21])[NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 186078Glycolaldehyde dimerHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 231567387-amino-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

Product 1

HCID 231567927-(2-hydroxyethylamino)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-oneYield 15.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

350 mg (1.15 mmol) of the 7-amino-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one obtained in Example 38 was dissolved in 11.5 ml of methanol, and thereafter, 1.15 ml of acetic acid and 552.5 mg (4.60 mmol) of glycolaldehyde dimer were added thereto. Thereafter, 722 mg (11.5 mmol) of sodium cyanoborohydride was added to the mixture under cooling on ice. The temperature of the mixture was increased to a room temperature, and the mixture was then stirred for 8 hours. Thereafter, a saturated sodium bicarbonate aqueous solution was added to the reaction solution, and the mixture was then extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and was then concentrated. The obtained residue was purified by silica gel column chromatography (methylene chloride:methanol=20:1 to 12:1), so as to obtain 61.8 mg (15%) of 7-(2-hydroxyethylamino)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one in the form of a yellow amorphous substance, as well as 369.3 mg (82%) of 7-[bis(2-hydroxyethyl)amino]-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one in the form of a yellow foaming substance.

Workup

  1. temperatureunder cooling on ice
  2. extractionthe mixture was then extracted with ethyl acetate
  3. dry with materialThe extract was dried over anhydrous sodium sulfate
  4. concentrationwas then concentrated
  5. customThe obtained residue was purified by silica gel column chromatography (methylene chloride:methanol=20:1 to 12:1)

Sources & evidence

ORD record
ord-df6ec15ce984454192e0de5b922ad43b
Source dataset
uspto-grants-2012_03
Patent number
US08143274B2

Reaction notes

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