Sodium Hydroxide → (R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate

HRID 1529424노트

반응식

HRID 1529424 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14](S(C1C=CC(C)=CC=1)(=O)=O)[CH:13]=[C:12]2[C:28]1[CH:33]=[C:32]([O:34][CH3:35])[N:31]=[C:30]([NH:36][C@@H:37]2[CH2:42][CH2:41][CH2:40][N:39]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:38]2)[N:29]=1.[OH-].[Na+]>O1CCOCC1>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:28]1[CH:33]=[C:32]([O:34][CH3:35])[N:31]=[C:30]([NH:36][C@@H:37]2[CH2:42][CH2:41][CH2:40][N:39]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:38]2)[N:29]=1

참가 물질

4

반응물 2

HCID 14798Sodium HydroxideHCID 67959888(R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate

생성물 1

HCID 67959910(R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate수율 77.2%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

To a solution of (R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate (500 mg, 0.726 mmol) in dioxane (7 mL) was added 7M aq.NaOH (7 mL) and the mixture was heated at 90° C. for 6 h. The reaction was quenched with water and the suspension was filtered. The resulting solid was washed with water and dried. The crude product was purified with silica gel chromatography (eluting with 50% EtOAc in Hexanes) to give (R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate (300 mg, 77%). MS (ESI, pos. ion) m/z: 536.0 (M+1); 1H-NMR (400 MHz CDCl3): δ ppm: 8.63 (s, 1H), 8.41 (brs, 1H), 7.90 (s, 1H), 7.65-7.77 (m, 1H), 7.48-7.57 (m, 2H), 7.30-7.35 (m, 1H), 6.99-7.03 (m, 2H), 6.43 (s, 1H), 5.00 (s, 1H), 4.09-4.13 (m, 1H), 3.92 (s, 3H), 3.33-3.73 (m, 4H), 2.05 (s, 1H), 1.63-1.72 (m, 1H), 1.38 (s, 9H), 0.86-0.90 (m, 1H).

후처리

  1. customThe reaction was quenched with water
  2. filtrationthe suspension was filtered
  3. washThe resulting solid was washed with water
  4. customdried
  5. customThe crude product was purified with silica gel chromatography (eluting with 50% EtOAc in Hexanes)

출처 및 근거

ORD 기록
ord-70bf98da246640d3b8adb24e6dccfb5d
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09090593B2

반응 노트

불러오는 중…