(R)-tert-butyl 3-(6-(5-(6-isopropoxy-pyrazin-2-yl)-1-tosyl-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate → (R)-tert-butyl 3-(6-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate

HRID 1529313ノート

反応式

HRID 1529313 の反応式
[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16](S(C2C=CC(C)=CC=2)(=O)=O)[CH:15]=[C:14]3[C:30]2[N:35]=[C:34]([NH:36][C@@H:37]3[CH2:42][CH2:41][CH2:40][N:39]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:38]3)[CH:33]=[N:32][CH:31]=2)[CH:8]=[N:7][CH:6]=1)([CH3:3])[CH3:2]>O1CCOCC1.[OH-].[Na+]>[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[C:14]3[C:30]2[N:35]=[C:34]([NH:36][C@@H:37]3[CH2:42][CH2:41][CH2:40][N:39]([C:43]([O:45][C:46]([CH3:48])([CH3:47])[CH3:49])=[O:44])[CH2:38]3)[CH:33]=[N:32][CH:31]=2)[CH:8]=[N:7][CH:6]=1)([CH3:3])[CH3:2]

参加物

4

反応物 1

HCID 67959931(R)-tert-butyl 3-(6-(5-(6-isopropoxy-pyrazin-2-yl)-1-tosyl-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate

生成物 1

HCID 67960038(R)-tert-butyl 3-(6-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate収率 93.1%

試薬・触媒・溶媒 2

HCID 14798Sodium Hydroxide溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a solution of (R)-tert-butyl 3-(6-(5-(6-isopropoxy-pyrazin-2-yl)-1-tosyl-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate (0.250 g, 0.365 mmol) in 1-4-dioxane (3.6 mL), 1N NaOH (3.6 mL) was added and heated at 100° C. for 2 h. The reaction mixture was quenched with ice cold water and precipitate was formed. The precipitate was collected by filtration, washed with ice cold water and dried to give pure (R)-tert-butyl 3-(6-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate (180 mg, 93%). MS (ESI, pos. ion) m/z: 530.0 (M+1). To a solution of (R)-tert-butyl 3-(6-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate (180 mg, 1.25 mmol) in EtOAc (5.0 mL) was treated with HCl in EtOAc (5.0 mL) and stirred at RT for 3 h. The reaction mixture was quenched with water, neutralized with NaHCO3, extracted with EtOAc. The organic layer was separated, dried over Na2SO4 and evaporated to dryness. The crude solid was re-crystallized in acetone to obtain (R)-6-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)-N-(piperidin-3-yl)pyrazin-2-amine. MS (ESI, pos. ion) m/z: 430.0 (M+1).

後処理

  1. customThe reaction mixture was quenched with ice cold water
  2. customprecipitate was formed
  3. filtrationThe precipitate was collected by filtration
  4. washwashed with ice cold water
  5. customdried

出典と根拠

ORDレコード
ord-9bf2853bd0c94a36a5ebb466ebffbf82
出典データセット
uspto-grants-2015_07
特許番号
US09090593B2

反応ノート

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