tert-butyl 4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylate → Tert-butyl 2'-isopropyl-7'-oxo-2',4',6',7'-tetrahydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridine]-1-carboxylate

HRID 880903Notes

Reaction equation

HRID 880903 reaction equation
I[C:2]1[C:6]([CH2:7][C:8]2([N:21]=[C:22]=[O:23])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:5][N:4]([CH:24]([CH3:26])[CH3:25])[N:3]=1.C([Li])(C)(C)C>O1CCCC1>[CH:24]([N:4]1[CH:5]=[C:6]2[C:2]([C:22](=[O:23])[NH:21][C:8]3([CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]3)[CH2:7]2)=[N:3]1)([CH3:26])[CH3:25]

Participants

4

Reactant 2

HCID 86664613tert-butyl 4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylateHCID 178418306HCID 178418306, compound

Product 1

HCID 67491432Tert-butyl 2'-isopropyl-7'-oxo-2',4',6',7'-tetrahydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridine]-1-carboxylateYield 63.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a −78° C. solution of tert-butyl 4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylate (280 mg, 0.59 mmol) in tetrahydrofuran (10 mL) was added t-butyl lithium (0.7 mL, 1.7 M in pentane), dropwise. After stirring for 30 minutes at −78° C. the mixture was warmed to 0° C., quenched with 20 mL saturated aqueous ammonium chloride, and stirred an additional 30 minutes at room temperature. The reaction mixture was diluted with 25 mL water and extracted with ethyl acetate (2×50 mL). The combined organics were dried over sodium sulfate, filtered and concentrated. The residue was then purified by flash chromatography (12-100% ethyl acetate/heptanes, 10 g silica gel) to yield tert-butyl 2′-isopropyl-7′-oxo-2′,4′,6′,7′-tetrahydrospiro[piperidine-4,5′-pyrazolo[3,4-c]pyridine]-1-carboxylate (130 mg) as a colorless solid. +ESI (M+H) 349.1; 1H NMR (500 MHz, CDCl3, δ): 7.28 (s, 1H), 5.78 (s, 1H), 4.57 (spt, J=6.6 Hz, 1H), 3.59 (m, 2H), 3.37 (m, 2H), 2.82 (s, 2H), 1.74 (m, 4H), 1.55 (d, J=6.6 Hz, 6H), 1.47 (s, 9H).

Workup

  1. temperaturewas warmed to 0° C.
  2. customquenched with 20 mL saturated aqueous ammonium chloride
  3. stirringstirred an additional 30 minutes at room temperature
  4. additionThe reaction mixture was diluted with 25 mL water
  5. extractionextracted with ethyl acetate (2×50 mL)
  6. dry with materialThe combined organics were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was then purified by flash chromatography (12-100% ethyl acetate/heptanes, 10 g silica gel)

Sources & evidence

ORD record
ord-3eb6712ea98f47bead292407497944d9
Source dataset
uspto-grants-2015_03
Patent number
US08993586B2

Reaction notes

Loading…