5-aminoisoquinolin-1(2H)-one → (Rac.)-5-{[4-(3-chloro-2-methoxy-4-methylphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentylidene]amino}isoquinolin-1(2h)-one

HRID 1443296Notes

Reaction equation

HRID 1443296 reaction equation
[Cl:1][C:2]1[C:3]([O:21][CH3:22])=[C:4]([C:9]([CH3:20])([CH3:19])[CH2:10][C:11]([OH:18])([C:14]([F:17])([F:16])[F:15])[CH:12]=O)[CH:5]=[CH:6][C:7]=1[CH3:8].[NH2:23][C:24]1[CH:33]=[CH:32][CH:31]=[C:30]2[C:25]=1[CH:26]=[CH:27][NH:28][C:29]2=[O:34]>CC1C=CC=CC=1C.[Cl-].[Na+].O.C(OCC)(=O)C.CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4]>[Cl:1][C:2]1[C:3]([O:21][CH3:22])=[C:4]([C:9]([CH3:19])([CH3:20])[CH2:10][C:11]([OH:18])([C:14]([F:17])([F:16])[F:15])[CH:12]=[N:23][C:24]2[CH:33]=[CH:32][CH:31]=[C:30]3[C:25]=2[CH:26]=[CH:27][NH:28][C:29]3=[O:34])[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

7

Reactant 2

HCID 20725-aminoisoquinolin-1(2H)-oneHCID 17989142(Rac.) 4-(3-chloro-2-methoxy-4-methylphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanal

Product 1

HCID 66657368(Rac.)-5-{[4-(3-chloro-2-methoxy-4-methylphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentylidene]amino}isoquinolin-1(2h)-oneYield 70.4%

Reagents, catalysts & solvents 4

HCID 11026Titanium isopropoxideCatalystHCID 7237O-XyleneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

225 mg (0.664 mmol) of (rac.) 4-(3-chloro-2-methoxy-4-methylphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanal, 106.3 mg (0.664 mmol) of 5-amino-isoquinolin-1(2H)-one and 0.39 ml (1.328 mmol) of titanium tetraisopropylate are stirred in 3.6 ml of o-xylene for two and one-half hours at 120° C. After cooling, the batch is poured into 15 ml of saturated brine and diluted with ethyl acetate. After 20 minutes of vigorous stirring at room temperature, it is filtered on a column, filled with Extrelute. The residue is on silica gel (mobile solvent:ethyl acetate/hexane). 224.7 mg (70.3%) of the desired compound is isolated.

Workup

  1. temperatureAfter cooling
  2. filtrationit is filtered on a column
  3. additionfilled with Extrelute

Sources & evidence

ORD record
ord-e656e581e7ce4492bfe322d99b92275f
Source dataset
uspto-grants-2010_02
Patent number
US07659297B2

Reaction notes

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