HCID 86664612, compound → HCID 67491791, compound

HRID 537092Notes

Reaction equation

HRID 537092 reaction equation
Br[C:2]1[N:6]([C:7]([CH3:10])([CH3:9])[CH3:8])[N:5]=[CH:4][C:3]=1[CH2:11][C:12]1([N:25]=[C:26]=[O:27])[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1.C([Li])(C)(C)C>C1COCC1>[C:7]([N:6]1[C:2]2[C:26](=[O:27])[NH:25][C:12]3([CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[CH2:14][CH2:13]3)[CH2:11][C:3]=2[CH:4]=[N:5]1)([CH3:9])([CH3:10])[CH3:8]

Participants

4

Reactant 2

HCID 86664612HCID 86664612, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 67491791HCID 67491791, compoundYield 74.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of tert-butyl 4-((5-bromo-1-tert-butyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylate (225 mg, 0.51 mmol) in THF (10 mL) was cooled to −78° C. and t-butyl lithium (0.6 mL, 1.7 M in pentane) was added, dropwise, over 2 minutes. The mixture was stirred 30 minutes at −78° C., warmed to 0° C., and then quenched with saturated aqueous NH4Cl (20 mL). The mixture was stirred 30 minutes at room temperature, diluted with water (25 mL), and then extracted with ethyl acetate (2×50 mL). The combined organics were dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography (12-100% ethyl acetate/heptane, 10 g silica gel) to yield 137 mg of tert-butyl 1′-tert-butyl-7′-oxo-1′,4′,6′,7′-tetrahydrospiro[piperidine-4,5′-pyrazolo[3,4-c]pyridine]-1-carboxylate as a colorless solid. +ESI (M-tBu) 307.2; 1H NMR (400 MHz, DMSO-d6, δ): 7.74 (s, 1H), 7.30 (s, 1H), 3.51 (m, 2H), 3.20 (m, 2H), 2.79 (s, 2H), 1.64 (s, 9H), 1.56 (t, J=5.8 Hz, 4H), 1.38 (s, 9H).

Workup

  1. temperaturewarmed to 0° C.
  2. customquenched with saturated aqueous NH4Cl (20 mL)
  3. stirringThe mixture was stirred 30 minutes at room temperature
  4. additiondiluted with water (25 mL)
  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 purified by flash chromatography (12-100% ethyl acetate/heptane, 10 g silica gel)

Sources & evidence

ORD record
ord-34ef7fcb6b814e0d9d2797053ced0b5e
Source dataset
uspto-grants-2014_10
Patent number
US08859773B2

Reaction notes

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