Bromine → Ethyl 3-bromo-1-(1-methylethyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

HRID 1522511Notes

Reaction equation

HRID 1522511 reaction equation
[CH3:1][CH:2]([N:4]1[C:8]2[N:9]=[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:11]=[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:7]=2[CH:6]=[N:5]1)[CH3:3].[Br:24]Br.C(=O)(O)[O-].[Na+]>C(O)(=O)C>[Br:24][C:6]1[C:7]2[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][C:10]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[N:9][C:8]=2[N:4]([CH:2]([CH3:3])[CH3:1])[N:5]=1

Participants

5

Reactant 3

HCID 24408Bromine2×HCID 516892Sodium BicarbonateHCID 46538388Ethyl 1-(1-methylethyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

Product 1

HCID 67124144Ethyl 3-bromo-1-(1-methylethyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl 1-(1-methylethyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate (120 mg, 0.388 mmol), was suspended in acetic acid (2 mL) followed by addition of bromine (26 μl, 0.504 mmol). The reaction mixture was stirred with heating at 80° C. After 1 h, a second portion of bromine was added (26 μl, 0.504 mmol) and the reaction mixture heated at 80° C. for an additional 2 h. After cooling to room temperature, the solution was added to a saturated aqueous solution of sodium bicarbonate (6 mL) and extracted with dichloromethane (2×10 mL) The combined organic layers were concentrated in vacuo. The crude product was purified by silica gel chromatography (eluent: EtOAc/Hexanes, 0-50% gradient). The product was collected as a white powder (112 mg, 74%). LCMS E-S (M+H)=388.0/390.2. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.18 (dd, J=1.52, 8.08 Hz, 2H), 8.00 (s, 1H), 7.48-7.58 (m, 3H), 5.47 (quin, J=6.76 Hz, 1H), 4.58 (q, J=7.16 Hz, 2H), 1.65 (d, J=6.82 Hz, 6H), 1.52 (t, J=7.20 Hz, 3H).

Workup

  1. temperaturethe reaction mixture heated at 80° C. for an additional 2 h
  2. temperatureAfter cooling to room temperature
  3. extractionextracted with dichloromethane (2×10 mL) The combined organic layers
  4. concentrationwere concentrated in vacuo
  5. customThe crude product was purified by silica gel chromatography (eluent: EtOAc/Hexanes, 0-50% gradient)
  6. customThe product was collected as a white powder (112 mg, 74%)

Sources & evidence

ORD record
ord-386ab8066eb1480dbb0d8ad16749bb5e
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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