Hydrochloric Acid → tert-Butyl {(3S)-1-[5-amino-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]piperidin-3-yl}carbamate

HRID 1499484Notes

Reaction equation

HRID 1499484 reaction equation
C(OC([NH:8][C:9]1[C:10]([N:27]2[CH2:32][CH2:31][CH2:30][C@H:29]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:28]2)=[C:11]2[CH:17]=[N:16][N:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[C:12]2=[N:13][CH:14]=1)=O)(C)(C)C.Cl.O1CCOCC1.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(N(CC)CC)C>C1COCC1.CCOC(C)=O>[NH2:8][C:9]1[C:10]([N:27]2[CH2:32][CH2:31][CH2:30][C@H:29]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:38])([CH3:37])[CH3:39])[CH2:28]2)=[C:11]2[CH:17]=[N:16][N:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[C:12]2=[N:13][CH:14]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 90495Di-tert-butyl dicarbonateHCID 86726718tert-butyl {(3S)-1-[5-[(tert-butoxycarbonyl)amino]-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]piperidin-3-yl}carbamate

Product 1

HCID 86726717tert-Butyl {(3S)-1-[5-amino-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]piperidin-3-yl}carbamateYield 73.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of tert-butyl {(3S)-1-[5-[(tert-butoxycarbonyl)amino]-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]piperidin-3-yl}carbamate (0.50 g, 0.90 mmol) and HCl in dioxane (4.0 M; 10 mL, 40 mmol) was stirred at room temperature for 2 h. The solution was then evaporated under reduced pressure. The resulting residue was dissolved in THF (10 mL), and di-tert-butyl dicarbonate (0.20 g, 0.92 mmol) in THF (5 mL) and triethylamine (0.37 g, 3.6 mmol) were added. The mixture was stirred at room temperature for 3 h. The reaction mixture was then diluted with EtOAc and the resulting solution was washed with aq. NaHCO3 and brine. The organic layer was then dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using CombiFlash® apparatus, eluting with 20 to 100% EtOAc in hexanes, to give 0.30 g (73%) of the sub-title compound. LCMS calc. for C24H33N6O3 (M+H)+: m/z=453.3. Found: 453.1.

Workup

  1. customThe solution was then evaporated under reduced pressure
  2. dissolutionThe resulting residue was dissolved in THF (10 mL)
  3. stirringThe mixture was stirred at room temperature for 3 h
  4. washthe resulting solution was washed with aq. NaHCO3 and brine
  5. dry with materialThe organic layer was then dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel using CombiFlash® apparatus
  8. washeluting with 20 to 100% EtOAc in hexanes

Sources & evidence

ORD record
ord-445963bac0ff4e1d9f6ec39bcd3f7da3
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

Loading…