Sodium hydride → HCID 67517324, compound

HRID 919648Notes

Reaction equation

HRID 919648 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[N:8][C:9]([NH2:10])=[C:4]2[CH:3]=[N:2]1.[H-].[Na+].CS(O[CH:18]1[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19]1)(=O)=O>CN(C=O)C>[NH2:10][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:1]([CH:22]3[CH2:23][CH2:18][CH2:19][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:21]3)[N:2]=[CH:3][C:4]=12

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 754201H-Pyrazolo[3,4-d]pyrimidin-4-amineHCID 568122N-Boc-3-mesyloxypiperidine

Product 1

HCID 67517324HCID 67517324, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1H-pyrazolo[3,4-d]pyrimidin-4-amine (675 mg, 5 mmol) in DMF (12 mL) was added NaH (60% wt in mineral oil, 240 mg, 6.0 mmol, 1.2 eq) and the mixture was stirred at rt for 0.5 h. The tert-butyl 3-((methylsulfonyl)oxy)piperidine-1-carboxylate (1.67 g, 6 mmol, 1.2 eq) was added and the mixture was heated to 100° C. for 16 h. The solution was cooled to rt and the reaction was quenched with brine (50 mL) and extracted with EtOAc (80 mL×4). The organic layers were dried over Na2SO4, concentrated in vacuo to afford a residue which was purified by column chromatography (silica gel, pure EtOAc) to give the title product (700 mg, yield: 50%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 9.24 (br s, 1H), 8.72 (br s, 1H), 8.41 (s, 1H), 8.33 (s, 1H), 4.67-4.62 (m, 1H), 4.05-3.58 (m, 3H), 3.40-3.33 (m, 1H), 2.98-2.95 (m 1H), 2.16-2.04 (m, 1H), 1.61-1.24 (m, 11H). ESI-MS (M+H+): 319.0.

Workup

  1. temperaturethe mixture was heated to 100° C. for 16 h
  2. temperatureThe solution was cooled to rt
  3. customthe reaction was quenched with brine (50 mL)
  4. extractionextracted with EtOAc (80 mL×4)
  5. dry with materialThe organic layers were dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customto afford a residue which
  8. customwas purified by column chromatography (silica gel, pure EtOAc)

Sources & evidence

ORD record
ord-f1aa4e6688914c8aada33906138585ea
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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