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

HRID 451208Notes

Reaction equation

HRID 451208 reaction equation
C(OC([C:6]1[C:7]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[CH3:24])=[C:8]2[CH:14]=[N:13][N:12]([CH2:15][CH3:16])[C:9]2=[N:10][CH:11]=1)=O)C.[OH-].[Na+].Cl.CC[N:30]([CH2:33]C)CC.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:42])=CC=1.[CH3:52][C:53]([OH:56])([CH3:55])[CH3:54]>CCO.C1COCC1>[C:53]([O:56][C:33](=[O:42])[NH:30][C:6]1[C:7]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[CH3:24])=[C:8]2[CH:14]=[N:13][N:12]([CH2:15][CH3:16])[C:9]2=[N:10][CH:11]=1)([CH3:55])([CH3:54])[CH3:52]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6386tert-ButanolHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 199401P,P-Diphenylphosphinic azideHCID 67440872HCID 67440872, compound

Product 1

HCID 67441355[1-Ethyl-4-(4-fluoro-2-methyl-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-carbamic acid tert-butyl esterYield 65.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of 1-ethyl-4-(4-fluoro-2-methyl-phenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester (3.6 g, 0.011 mol) in EtOH (20 mL) and THF (20 mL) was added an aqueous solution of NaOH (1N, 16.5 mL, 0.016 mol) 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 (90 mL) before Et3N (1.49 mL, 0.0107 mol), DPPA (diphenyl phosphorazidate, 2.94 g, 0.0107 mol) and tBuOH (4.0 mL, 0.0428 mol) 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 1/4) yielded 2.6 g (65%) of the title compound as a white solid. ES-MS m/e: 371.2 (M+H+).

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 1/4)

Sources & evidence

ORD record
ord-e1ddd001509c40408a4b32f25caaee94
Source dataset
uspto-grants-2013_07
Patent number
US08487102B2

Reaction notes

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