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Water → (S)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 80773
ノート
印刷プレビュー

反応式

HRID 80773 の反応式
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([CH3:50])=[C:8]([N:10]2[CH2:49][CH2:48][C:13]3[N:14]=[C:15]([C:28]4[CH:36]=[CH:35][CH:34]=[C:33]5[C:29]=4[C:30]([CH3:47])=[CH:31][N:32]5S(C4C=CC(C)=CC=4)(=O)=O)[N:16]=[C:17]([N:18]4[CH2:23][CH2:22][C@H:21]([O:24][CH3:25])[C:20]([CH3:27])([CH3:26])[CH2:19]4)[C:12]=3[CH2:11]2)[CH:9]=1)([CH3:3])[CH3:2].[OH-].[K+].[OH-].[NH4+].O>CO.ClCCl.[Cl-].[Na+].O>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([CH3:50])=[C:8]([N:10]2[CH2:49][CH2:48][C:13]3[N:14]=[C:15]([C:28]4[CH:36]=[CH:35][CH:34]=[C:33]5[C:29]=4[C:30]([CH3:47])=[CH:31][NH:32]5)[N:16]=[C:17]([N:18]4[CH2:23][CH2:22][C@H:21]([O:24][CH3:25])[C:20]([CH3:26])([CH3:27])[CH2:19]4)[C:12]=3[CH2:11]2)[CH:9]=1)([CH3:3])[CH3:2]
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

8

反応物 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 14923Ammonium HydroxideHCID 71240512(S)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

生成物 1

HCID 71240579(S)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
80 °C

実験手順

To a solution of (S)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (135 mg, 0.195 mmol) in methanol (2 mL) in a microwave vial was added KOH (100 mg, 1.75 mmol) followed by 28% ammonium hydroxide in water (1 mL, 7.25 mmol). The vial was sealed and heated via microwave irradiation at 80° C. for 75 minutes. The reaction mixture was cooled to room temperature and diluted with dichloromethane and brine. The layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The organic layers were combined, dried over Na2SO4, filtered, and concentrated. The resulting residue was purified by silica gel flash chromatography (0-70% ethyl acetate/heptanes) to furnish (S)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.92 (s, 3 H) 0.98 (s, 3 H) 1.18 (d, J=6.8 Hz, 6 H) 1.51-1.62 (m, 1 H) 1.91-1.99 (m, 1 H) 2.01 (s, 3 H) 2.21 (s, 3 H) 2.78-2.88 (m, 2 H) 2.91-3.08 (m, 4 H) 3.29 (s, 3 H) 3.31-3.41 (m, 3 H) 3.60-3.71 (m, 1 H) 4.07 (s, 2 H) 6.86 (d, J=7.3 Hz, 1 H) 6.96 (s, 1 H) 7.07-7.15 (m, 3 H) 7.20 (d, J=7.1 Hz, 1H) 7.41 (d, J=7.8 Hz, 1 H) 10.89 (br. s., 1 H); MS (ESI+) m/z 538.4 (M+H)+.

後処理

  1. customThe vial was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted two additional times with dichloromethane
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by silica gel flash chromatography (0-70% ethyl acetate/heptanes)

出典と根拠

ORDレコード
ord-c39960c2e0f545feb6664605dbf13671
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08846656B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート