Water → (5S)-4-(4,4-Difluorocyclohexyl)-2-[1-(5-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}pyrimidin-2-yl)piperidin-4-yl]-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol

HRID 632614노트

반응식

HRID 632614 반응식
[F:1][C:2]1([F:46])[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[C@@H:16]([OH:18])[CH2:15][C:14]([CH3:20])([CH3:19])[CH2:13][C:12]=3[N:11]=[C:10]([CH:21]3[CH2:26][CH2:25][N:24]([C:27]4[N:32]=[CH:31][C:30]([OH:33])=[CH:29][N:28]=4)[CH2:23][CH2:22]3)[C:9]=2[C@@H:34]([F:45])[C:35]2[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][CH:36]=2)[CH2:4][CH2:3]1.C1(C)C=CC(S(O[CH2:57][C@@H:58]2[CH2:62][O:61][C:60]([CH3:64])([CH3:63])[O:59]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[F:46][C:2]1([F:1])[CH2:3][CH2:4][CH:5]([C:8]2[C:17]3[C@@H:16]([OH:18])[CH2:15][C:14]([CH3:19])([CH3:20])[CH2:13][C:12]=3[N:11]=[C:10]([CH:21]3[CH2:22][CH2:23][N:24]([C:27]4[N:32]=[CH:31][C:30]([O:33][CH2:57][C@@H:58]5[CH2:62][O:61][C:60]([CH3:64])([CH3:63])[O:59]5)=[CH:29][N:28]=4)[CH2:25][CH2:26]3)[C:9]=2[C@@H:34]([F:45])[C:35]2[CH:36]=[CH:37][C:38]([C:41]([F:43])([F:42])[F:44])=[CH:39][CH:40]=2)[CH2:6][CH2:7]1

참가 물질

6

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 2723760(S)-(+)-2,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-ToluenesulfonateHCID 56598385(5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-hydroxypyrimidin-2-yl)piperidin-4-yl]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol

생성물 1

HCID 89531585(5S)-4-(4,4-Difluorocyclohexyl)-2-[1-(5-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}pyrimidin-2-yl)piperidin-4-yl]-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol수율 82%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
90 °C

실험 절차

To a solution of 95.0 mg (0.146 mmol) of (5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-hydroxypyrimidin-2-yl)piperidin-4-yl]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol, which was prepared by a method similar to that of Reference Example 23, in 0.4 ml of N,N-dimethylformamide, 92.4 mg (0.322 mmol) of (S)-2,2-dimethyl-1,3-dioxolan-4-ylmethyl p-toluenesulfonate and 54.2 mg (0.392 mmol) of potassium carbonate were added, and the mixture was stirred at 90° C. for 5 hours. After completion of the reaction, the reaction solution was poured into water and extracted with toluene twice. The obtained organic phases were combined and washed with saturated sodium chloride aqueous solution, and then the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography [n-hexane/ethyl acetate=80/20-59/41 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure to provide 91.3 mg of the title compound as a white solid (yield: 82%).

후처리

  1. customAfter completion of the reaction
  2. extractionextracted with toluene twice
  3. washwashed with saturated sodium chloride aqueous solution
  4. distillationthe solvent was distilled off under reduced pressure
  5. concentrationwas concentrated under reduced pressure

출처 및 근거

ORD 기록
ord-9ed43e91e76f415c99047929ca93f59f
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321747B2

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