Hydrochloric Acid → [1-Benzyl-4-(4-fluoro-2-methyl-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-carbamic acid tert-butyl ester

HRID 451216Notes

Reaction equation

HRID 451216 reaction equation
C(OC([C:6]1[C:7]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=2[CH3:29])=[C:8]2[CH:14]=[N:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:9]2=[N:10][CH:11]=1)=O)C.[OH-].[Na+].Cl.CC[N:35]([CH2:38]C)CC.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:47])=CC=1.[CH3:57][C:58]([OH:61])([CH3:60])[CH3:59]>CCO.C1COCC1>[C:58]([O:61][C:38](=[O:47])[NH:35][C:6]1[C:7]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=2[CH3:29])=[C:8]2[CH:14]=[N:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:9]2=[N:10][CH:11]=1)([CH3:60])([CH3:59])[CH3:57]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6386tert-ButanolHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 199401P,P-Diphenylphosphinic azideHCID 674406501-Benzyl-4-(4-fluoro-2-methyl-phenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester

Product 1

HCID 67440908[1-Benzyl-4-(4-fluoro-2-methyl-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-carbamic acid tert-butyl esterYield 58.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of 1-benzyl-4-(4-fluoro-2-methyl-phenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester (4.0 g, 10.3 mmol) in EtOH (20 mL) and THF (20 mL) was added an aqueous solution of NaOH (1N, 20 mL, 20.0 mmol) and the mixture was heated at 50° C. for 3 hours. After cooling down to RT, the mixture was acidified with aqueous HCl (1N) until pH reached 3 and the product extracted with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated to give the crude acid which was used directly in the next step without further purification. The residue was taken up in THF (20 mL) before Et3N (1.42 mL, 10.3 mmol), DPPA (diphenyl phosphorazidate, 2.83 g, 10.3 mmol) and tBuOH (3.85 mL, 41.1 mmol) were added. The reaction mixture was heated at 60° C. for 7 hours, volatiles were then partially evaporated, and the concentrated solution poured onto EtOAc (200 mL) and washed with H2O. The organic layer was dried over Na2SO4, and purification by column chromatography (SiO2, EtOAc/Heptane 1/5) yielded 2.6 g (58%) of the title compound as a white solid.

Workup

  1. temperatureAfter cooling down to RT
  2. extractionthe product extracted with EtOAc
  3. dry with materialThe combined organic phases were dried over Na2SO4
  4. concentrationconcentrated
  5. customto give the crude acid which
  6. customwas used directly in the next step without further purification
  7. additionwere added
  8. temperatureThe reaction mixture was heated at 60° C. for 7 hours
  9. customvolatiles were then partially evaporated
  10. additionthe concentrated solution poured onto EtOAc (200 mL)
  11. washwashed with H2O
  12. dry with materialThe organic layer was dried over Na2SO4, and purification by column chromatography (SiO2, EtOAc/Heptane 1/5)

Sources & evidence

ORD record
ord-1299ea86a65c4783828d0245b7e28a36
Source dataset
uspto-grants-2013_07
Patent number
US08487102B2

Reaction notes

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