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

HRID 1443303Notes

Reaction equation

HRID 1443303 reaction equation
ClC1C=CC(C(C)(C)CC(O)(C(F)(F)F)C=O)=C(OC)C=1F.C(O[C:26](=O)[C:27]([C:43]([F:46])([F:45])[F:44])([OH:42])[CH2:28][C:29]([C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[C:34]([F:39])[C:33]=1[O:40][CH3:41])([CH3:31])[CH3:30])C.[NH2:48][C:49]1[CH:58]=[CH:57][CH:56]=[C:55]2[C:50]=1[CH:51]=[CH:52][NH:53][C:54]2=[O:59]>CC1C=CC=CC=1C.C(OCC)(=O)C.[Cl-].[Na+].O.CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4]>[Cl:38][C:35]1[CH:36]=[CH:37][C:32]([C:29]([CH3:31])([CH3:30])[CH2:28][C:27]([OH:42])([C:43]([F:46])([F:44])[F:45])[CH:26]=[N:48][C:49]2[CH:58]=[CH:57][CH:56]=[C:55]3[C:50]=2[CH:51]=[CH:52][NH:53][C:54]3=[O:59])=[C:33]([O:40][CH3:41])[C:34]=1[F:39]

Participants

8

Reactant 3

HCID 20725-aminoisoquinolin-1(2H)-oneHCID 17989096(rac.) 4-(4-Chloro-3-fluoro-2-methoxyphenyl)-4-methyl-2-(trifluoromethyl)-2-hydroxy-pentanoic acid ethyl esterHCID 17989212(Rac.) 4-(4-chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanal

Product 1

HCID 17989293(Rac.) 5-{[4-(4-chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentylidene]amino}isoquinolin-1(2h)-oneYield 30.4%

Reagents, catalysts & solvents 4

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

Procedure

560 mg of the mixture that consists of (rac.) 4-(4-chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanal and (rac.) 4-(4-chloro-3-fluoro-2-methoxyphenyl)-4-methyl-2-(trifluoromethyl)-2-hydroxy-pentanoic acid ethyl ester (since aldehyde constitutes two-thirds of the mixture, 560.2 mg of the mixture corresponds to 336.1 mg (0.981 mmol) of aldehyde) is heated for two hours to 120° C. with 157.1 mg (0.981 mmol) of 5-amino-isoquinolin-1(2H)-one and 0.557 mg (1.962 mmol) of titanium tetraisopropylate in 6 ml of o-xylene. After cooling, the batch is diluted with ethyl acetate and mixed with brine. The organic phase is separated and worked up as usual. After chromatography on a Flashmaster, 144.7 mg (30.4%) of the desired compound is obtained (relative to the proportion of aldehyde in the mixture).

Workup

  1. temperatureAfter cooling
  2. customThe organic phase is separated

Sources & evidence

ORD record
ord-0bafb551c7d146cd8b974eb9eb84d86c
Source dataset
uspto-grants-2010_02
Patent number
US07659297B2

Reaction notes

Loading…