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Dichloromethane → 8-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-3-oxa-8-azabicyclo[3.2.1]octan-6-ol

HRID 1972451
ノート
印刷プレビュー

反応式

HRID 1972451 の反応式
C([O:8][CH:9]1[CH2:15][CH:14]2[N:16]([CH2:17][C@H:18]3[CH2:23][N:22]([S:24]([C:27]4[S:28][CH:29]=[CH:30][CH:31]=4)(=[O:26])=[O:25])[CH2:21][CH2:20][N:19]3[C:32]3[CH:37]=[CH:36][C:35]([C:38]([OH:44])([CH3:43])[C:39]([F:42])([F:41])[F:40])=[CH:34][CH:33]=3)[CH:10]1[CH2:11][O:12][CH2:13]2)C1C=CC=CC=1.C(Cl)Cl.B(Cl)(Cl)Cl>CO>[S:28]1[CH:29]=[CH:30][CH:31]=[C:27]1[S:24]([N:22]1[CH2:21][CH2:20][N:19]([C:32]2[CH:37]=[CH:36][C:35]([C:38]([OH:44])([CH3:43])[C:39]([F:42])([F:41])[F:40])=[CH:34][CH:33]=2)[C@@H:18]([CH2:17][N:16]2[CH:10]3[CH:9]([OH:8])[CH2:15][CH:14]2[CH2:13][O:12][CH2:11]3)[CH2:23]1)(=[O:25])=[O:26]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 6344DichloromethaneHCID 25135Boron TrichlorideHCID 665827812-(4-((2S)-2-((6-(benzyloxy)-3-oxa-8-azabicyclo[3.2.1]oct-8-yl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

生成物 1

HCID 569323728-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-3-oxa-8-azabicyclo[3.2.1]octan-6-ol収率 69.6%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
0 °C

実験手順

A 100 mL round-bottomed flask was charged with 2-(4-((2S)-2-((6-(benzyloxy)-3-oxa-8-azabicyclo[3.2.1]oct-8-yl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.350 g, 0.537 mmol) and 5 mL of CH2Cl2. After cooling to 0° C., BCl3 (1M in CH2Cl2, 2.15 mL, 2.15 mmol, Sigma-Aldrich, St. Louis, Mo.) was added drop-wise. This mixture was allowed to warm to room temperature then stirred for an additional 15 min. 10 mL of MeOH was added and the mixture was concentrated onto silica gel and purified via column chromatography (0-7% MeOH in CH2Cl2) to give 8-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-3-oxa-8-azabicyclo[3.2.1]octan-6-ol (endo) (0.210 g) as a mixture of four isomers. 1H NMR (400 MHz, CD3OD) δ 7.92 (d, J=4.9 Hz, 1H), 7.67 (d, J=3.5 Hz, 1H), 7.54 (t, J=7.2 Hz, 2H), 7.28 (t, J=5.3 Hz, 1H), 7.06 (t, J=9.1 Hz, 2H), 4.43-4.62 (m, 2H), 3.39-4.24 (m, 13H), 2.66-2.98 (m, 2H), 2.55 (d, J=3.91 Hz, 1H), 1.69 (br. s., 3H). m/z (ESI, +ve ion) 562.1 (M+H)+. GK-GKRP IC50 (Binding)=0.028 μM; GK-GKRP EC50 (LC MS/MS-2)=0.031 μM.

後処理

  1. temperatureto warm to room temperature
  2. concentrationthe mixture was concentrated onto silica gel
  3. custompurified via column chromatography (0-7% MeOH in CH2Cl2)

出典と根拠

ORDレコード
ord-b1b902ce0ca74949b2c69c3001ad3918
出典データセット
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08431563B2

反応ノート

読み込み中…

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