Potassium Carbonate → HCID 71604910、化合物

HRID 632618ノート

反応式

HRID 632618 の反応式
[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][CH2:58][CH2:59][S:60]([CH3:63])(=[O:62])=[O:61])(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].ClC1N=CC(O)=CN=1>CN(C)C=O.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][CH2:58][CH2:59][S:60]([CH3:63])(=[O:62])=[O:61])=[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

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 145957002-Chloro-5-pyrimidinolHCID 22732325(3-(Methylsulfonyl)propyl 4-methylbenzenesulfonateHCID 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

生成物 1

HCID 71604910HCID 71604910、化合物収率 80%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

To a solution of 145 mg (0.224 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 0.7 ml of N,N-dimethylformamide, 130 mg (0.445 mmol) of 3-(methylsulfonyl)propyl p-toluenesulfonate and 135 mg (0.977 mmol) of potassium carbonate were added, and the mixture was stirred at 80° C. for 4 hours. 44 mg (0.337 mmol) of 2-chloro-5-hydroxypyrimidine was further added thereto, and the mixture was stirred at 80° C. for 3 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=55/45-25/75 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure to provide 137.0 mg of the title compound as a white solid (yield: 80%).

後処理

  1. stirringthe mixture was stirred at 80° C. for 3 hours
  2. customAfter completion of the reaction
  3. extractionextracted with toluene twice
  4. washwashed with saturated sodium chloride aqueous solution
  5. distillationthe solvent was distilled off under reduced pressure
  6. concentrationwas concentrated under reduced pressure

出典と根拠

ORDレコード
ord-e441b525801345b69fd75df2a1ad9945
出典データセット
uspto-grants-2016_04
特許番号
US09321747B2

反応ノート

読み込み中…