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Methanol → 1-(((5S,7S)-3-(5-(2-(2-methoxyethoxy)propan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

HRID 715547
ノート
印刷プレビュー

反応式

HRID 715547 の反応式
[OH:1][CH2:2][CH2:3][O:4][C:5]([C:8]1[N:9]=[CH:10][C:11]([N:14]2[CH2:18][C@@:17]3([CH2:23][CH2:22][CH2:21][C@@:20]([CH2:25][N:26]4[C:30]5[CH:31]=[C:32]([C:35]#[N:36])[CH:33]=[CH:34][C:29]=5[N:28]=[CH:27]4)([CH3:24])[CH2:19]3)[O:16][C:15]2=[O:37])=[N:12][CH:13]=1)([CH3:7])[CH3:6].[H-].[Na+].[CH3:40]I.CO>CN(C)C=O.CC(O)=O>[CH3:40][O:1][CH2:2][CH2:3][O:4][C:5]([C:8]1[N:9]=[CH:10][C:11]([N:14]2[CH2:18][C@@:17]3([CH2:23][CH2:22][CH2:21][C@@:20]([CH2:25][N:26]4[C:30]5[CH:31]=[C:32]([C:35]#[N:36])[CH:33]=[CH:34][C:29]=5[N:28]=[CH:27]4)([CH3:24])[CH2:19]3)[O:16][C:15]2=[O:37])=[N:12][CH:13]=1)([CH3:7])[CH3:6]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 887MethanolHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 712275921-(((5S,7S)-3-(5-(2-(2-hydroxyethoxy)propan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

生成物 1

HCID 712276381-(((5S,7S)-3-(5-(2-(2-methoxyethoxy)propan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile
収率 40.3%

試薬・触媒・溶媒 2

HCID 176Acetic Acid触媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 1-(((5S,7S)-3-(5-(2-(2-hydroxyethoxy)propan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (40 mg, 0.079 mmol) in N,N-Dimethylformamide (DMF) (1 mL) was added sodium hydride (4.76 mg, 0.119 mmol) at RT. After 10 minutes, MeI (0.020 mL, 0.317 mmol) was added and stirred for an hour. To the mixture was added 0.5 mL MeOH and 2 drops 5% AcOH to buffer to pH 10, then filtered and purified by reverse phase HPLC (Waters Sunfire 30×150 mm Acetonitrile:Water 0.1% TFA 50-100%, 50 mL/min, 15 min). The product was free based with PL-HCO3 resin SPE to yield 1-(((5S,7S)-3-(5-(2-(2-methoxyethoxy)propan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile as a white solid (16.5 mg, 39%). 1H NMR (400 MHz, DMSO-d6) δ 9.23 (d, J=1.51 Hz, 1H), 8.57 (d, J=1.51 Hz, 1H), 8.50 (s, 1H), 8.39 (d, J=0.75 Hz, 1H), 7.84 (d, J=8.53 Hz, 1H), 7.60 (dd, J=8.41, 1.38 Hz, 1H), 4.12-4.23 (m, 2H), 3.88 (dd, J=23.09, 10.29 Hz, 2H), 3.43-3.48 (m, 2H), 3.34-3.39 (m, 2H), 3.26 (s, 3H), 2.00 (d, J=13.30 Hz, 1H), 1.89 (d, J=14.31 Hz, 1H), 1.58-1.77 (m, 3H), 1.43-1.56 (m, 8H), 1.30-1.41 (m, 1H), 1.07 (s, 3H). MS (m/z) 519.3 (M+H+).

後処理

  1. filtrationfiltered
  2. custompurified by reverse phase HPLC (Waters Sunfire 30×150 mm Acetonitrile:Water 0.1% TFA 50-100%, 50 mL/min, 15 min)

出典と根拠

ORDレコード
ord-3a28bd81c6374a9d8e5a2601b05d6d8f
出典データセット
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09187464B2

反応ノート

読み込み中…

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