tert-butyl 4-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylate → Tert-butyl 1'-isopropyl-7'-oxo-1',4',6',7'-tetrahydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridine]-1-carboxylate

HRID 711025노트

반응식

HRID 711025 반응식
Br[C:2]1[N:6]([CH:7]([CH3:9])[CH3:8])[N:5]=[CH:4][C:3]=1[CH2:10][C:11]1([N:24]=[C:25]=[O:26])[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.C([Li])(C)(C)C>CC1CCCO1>[CH:7]([N:6]1[C:2]2[C:25](=[O:26])[NH:24][C:11]3([CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:13][CH2:12]3)[CH2:10][C:3]=2[CH:4]=[N:5]1)([CH3:8])[CH3:9]

참가 물질

4

반응물 2

HCID 71507904tert-butyl 4-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylateHCID 178418306HCID 178418306, 화합물

생성물 1

HCID 67491663Tert-butyl 1'-isopropyl-7'-oxo-1',4',6',7'-tetrahydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridine]-1-carboxylate수율 67%

시약·촉매·용매 1

HCID 73012-Methyltetrahydrofuran용매

실험 절차

To a mixture of tert-butyl 4-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylate (1.4 g, 3.3 mmol) in 2-methyl tetrahydrofuran (10 mL) was added t-butyl lithium (1.7 M in hexane, 4.3 mL, 7.2 mmol) at −78° C., under argon. After the addition was complete the mixture was allowed to warm to room temperature and was stirred for 18 hours. The mixture was quenched with water (10 mL) and then diluted with ethyl acetate (20 mL). The layers were separated and the organic layer was washed with brine (10 mL), dried over sodium sulfate, filtered and the solvent removed in vacuo. The crude product was purified by flash column chromatography to give tert-butyl 1′-isopropyl-7′-oxo-1′,4′,6′,7′-tetrahydrospiro[piperidine-4,5′-pyrazolo[3,4-c]pyridine]-1-carboxylate (0.77 g, 67%). +ESI (M+H) 374.1; 1H NMR (300 MHz, CDCl3, δ): 7.34 (s, 1H), 6.35 (s, 1H), 5.45 (m, 1H), 3.57 (m, 2H), 3.42 (m, 2H), 2.79 (s, 2H), 1.70 (m, 4H), 1.45 (m, 15H).

후처리

  1. additionAfter the addition
  2. customThe mixture was quenched with water (10 mL)
  3. additiondiluted with ethyl acetate (20 mL)
  4. customThe layers were separated
  5. washthe organic layer was washed with brine (10 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. customThe crude product was purified by flash column chromatography

출처 및 근거

ORD 기록
ord-f88516fde2054d22b170f594518c1de1
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181252B2

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