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 420638노트

반응식

HRID 420638 반응식
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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 11026Titanium isopropoxide촉매HCID 7237O-Xylene용매HCID 8857Ethyl Acetate용매HCID 57417360Sodium chloride; water용매

실험 절차

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 the aldehyde constitutes two thirds in the mixture, the 560.2 mg 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 aldehyde portion in the mixture).

후처리

  1. temperatureAfter cooling
  2. customThe organic phase is separated

출처 및 근거

ORD 기록
ord-5d9b6b1bbb614c8fb31a56d4b1fe109d
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08097627B2

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