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

HRID 880895ノート

反応式

HRID 880895 の反応式
Br[C:2]1[N:6](C(C)C)[N:5]=[CH:4][C:3]=1[CH2:10][C:11]1([N:24]=[C:25]=O)[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>[NH:6]1[C:2]2=[CH:25][NH:24][C:11]3([CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:23])[CH3:21])=[O:18])[CH2:15][CH2:16]3)[CH2:10][CH:3]2[CH2:4][NH:5]1

参加物

4

反応物 2

HCID 71507904tert-butyl 4-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylateHCID 178418306HCID 178418306、化合物

生成物 1

HCID 117818533Tert-butyl tetrahydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridine]-1-carboxylate収率 79.3%

試薬・触媒・溶媒 1

HCID 73012-Methyltetrahydrofuran溶媒

実験手順

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 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).

後処理

  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

出典と根拠

ORDレコード
ord-59f19b5d2c064fe38b95b5e2d0afb008
出典データセット
uspto-grants-2015_03
特許番号
US08993586B2

反応ノート

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