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Ethyl Acetate → (S)-methyl 1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-3-carboxylate

HRID 1028022
ノート
印刷プレビュー

反応式

HRID 1028022 の反応式
[CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][C:11]([F:16])=[C:12]([CH3:15])[CH:13]=3)[C:8]([C:17]([O:19][CH3:20])=[O:18])=[C:7]2B(O)O)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:25]1[N:30]=[CH:29][C:28]([S:31]([NH:34][C@@H:35]([CH3:40])[C:36]([F:39])([F:38])[F:37])(=[O:33])=[O:32])=[CH:27][CH:26]=1.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>C(#N)C>[CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][C:11]([F:16])=[C:12]([CH3:15])[CH:13]=3)[C:8]([C:17]([O:19][CH3:20])=[O:18])=[C:7]2[C:25]2[CH:26]=[CH:27][C:28]([S:31](=[O:33])(=[O:32])[NH:34][C@@H:35]([CH3:40])[C:36]([F:38])([F:37])[F:39])=[CH:29][N:30]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 667309151-cyclopentyl-5-fluoro-3-(methoxycarbonyl)-6-methyl-1H-indol-2-ylboronic acidHCID 86665920(S)-6-chloro-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide

生成物 1

HCID 66730643(S)-methyl 1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-3-carboxylate
収率 54%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

A mixture of 1-cyclopentyl-5-fluoro-3-(methoxycarbonyl)-6-methyl-1H-indol-2-ylboronic acid (2.2 mmol), (S)-6-chloro-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (0.53 g, 1.83 mmol), PdCl2dppf (0.15 g, 0.183 mmol), aq. K2CO3 (2.0 M, 3.6 mL, 7.2 mmol) in acetonitrile (10 mL) was stirred at room temperature over the weekend. The mixture was treated with ethyl acetate and washed with water and brine and then concentrated. The residue was purified by flash chromatography with 0-15% ethyl acetate in CH2Cl2 to provide (S)-methyl 1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-3-carboxylate (0.52 g, 54%). MS m/z 528.2 M+H+; 1H NMR (500 MHz, CDCl3): δ 9.21 (1H, d, J=1.8 Hz), 8.25 (1H, dd, J=8.2 Hz, J=2.2 Hz), 7.87 (1H, d, J=10.6 Hz), 7.73 (1H, d, J=8.2 Hz), 7.27 (1H, d, J=5.2 Hz), 5.09 (1H, d, J=9.6 Hz), 4.39-4.31 (1H, m), 4.17-4.10 (1H, m), 3.70 (3H, s), 2.44 (3H, d, J=1.8 Hz), 2.41-2.36 (2H, m), 2.20-1.96 (4H, m), 1.67-1.63 (2H, m), 1.45 (3H, d, J=7.0 Hz).

後処理

  1. washwashed with water and brine
  2. concentrationconcentrated
  3. customThe residue was purified by flash chromatography with 0-15% ethyl acetate in CH2Cl2

出典と根拠

ORDレコード
ord-f43a549628114a8abe525be933bec518
出典データセット
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08735414B2

反応ノート

読み込み中…

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