(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 1529313노트

반응식

HRID 1529313 반응식
[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]

참가 물질

4

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 14798Sodium Hydroxide용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-9bf2853bd0c94a36a5ebb466ebffbf82
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09090593B2

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