Sodium Hydroxide → Tert-butyl 2'-(tert-butyl)-7'-oxo-2',4',6',7'-tetrahydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridine]-1-carboxylate

HRID 537114Notes

Reaction equation

HRID 537114 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:17][C:18]2[C:19](C(O)=O)=[N:20][N:21]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:22]=2)([N:14]=[C:15]=[O:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl.CN(C)CCCN=C=NCC>O1CCCC1.ClCCl>[C:23]([N:21]1[CH:22]=[C:18]2[C:19]([C:15](=[O:16])[NH:14][C:11]3([CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][CH2:12]3)[CH2:17]2)=[N:20]1)([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 866646154-((1-(tert-butoxycarbonyl)-4-isocyanatopiperidin-4-yl)methyl)-1-tert-butyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 67491594Tert-butyl 2'-(tert-butyl)-7'-oxo-2',4',6',7'-tetrahydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridine]-1-carboxylateYield 43.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-((1-(tert-butoxycarbonyl)-4-isocyanatopiperidin-4-yl)methyl)-1-tert-butyl-1H-pyrazole-3-carboxylic acid (180 mg, 0.44 mmol) in tetrahydrofuran (5 mL) was treated with 2 N aqueous sodium hydroxide (0.664 mL, 1.33 mmol). The mixture was stirred 3 hours at room temperature, tetrahydrofuran and water were removed on a rotary evaporator and the resultant colorless solid was slurried in acetonitrile (10 mL) and then concentrated to dryness. The trituration was repeated twice more from acetonitrile (10 mL). The resultant colorless solid was taken up in dichloromethane (10 mL) and treated with (3-(dimethylamino)propyl)ethyl carbodiimide hydrochloride (170 mg, 0.89 mmol). The mixture was stirred 18 hours at room temperature and then diluted with dichloromethane (50 mL) and washed with water (30 mL). The organic phase was dried over sodium sulfate, filtered and concentrated. The residue was then purified by flash chromatography (30-100% ethyl acetate/heptanes, 10 g silica gel) to yield tert-butyl 2′-tert-butyl-7′-oxo-2′,4′,6′,7′-tetrahydrospiro[piperidine-4,5′-pyrazolo[3,4-c]pyridine]-1-carboxylate (70 mg) as a colorless solid. +ESI (M+H) 363.3; 1H NMR (400 MHz, DMSO-d6, δ): 7.68 (s, 1H), 7.57 (s, 1H), 3.47 (m, 2H), 3.20 (m, 2H), 2.73 (s, 2H), 1.53 (t, J=5.7 Hz, 4H), 1.49 (s, 9H), 1.36 (s, 9H).

Workup

  1. customtetrahydrofuran and water were removed on a rotary evaporator
  2. concentrationconcentrated to dryness
  3. stirringThe mixture was stirred 18 hours at room temperature
  4. washwashed with water (30 mL)
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was then purified by flash chromatography (30-100% ethyl acetate/heptanes, 10 g silica gel)

Sources & evidence

ORD record
ord-930abf2bce6a4ef4bea102123090a8f3
Source dataset
uspto-grants-2014_10
Patent number
US08859773B2

Reaction notes

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