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 880895Notes

Reaction equation

HRID 880895 reaction equation
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

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-59f19b5d2c064fe38b95b5e2d0afb008
Source dataset
uspto-grants-2015_03
Patent number
US08993586B2

Reaction notes

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