Potassium Carbonate → HCID 178509953, compound

HRID 1952386Notes

Reaction equation

HRID 1952386 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:12](=[O:19])[NH:13][CH:14]=[C:15]([Cl:18])[C:16]=2[Cl:17])[CH:9]=1)[C:5]#[N:6].Br[CH2:21][C:22]1[C:30]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[N:24](C(OC(C)(C)C)=O)[N:23]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:12](=[O:19])[N:13]([CH2:21][C:22]3[C:30]4[C:25](=[N:26][CH:27]=[CH:28][CH:29]=4)[NH:24][N:23]=3)[CH:14]=[C:15]([Cl:18])[C:16]=2[Cl:17])[CH:9]=1)[C:5]#[N:6]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 10828872tert-Butyl 3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylateHCID 68510372HCID 68510372, compound

Product 1

HCID 178509953HCID 178509953, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 3-chloro-5-[(4,5-dichloro-2-oxo-1,2-dihydropyridin-3-yl)oxy]benzonitrile (49 mg, 0.155 mmol) in DMF (1 mL) was added tert-butyl 3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylate (48.5 mg, 0.155 mmol) and potassium carbonate (21.46 mg, 0.155 mmol) and the mixture heated at 55° C. for 30 minutes. After this time, the reaction mixture was allowed to cool to room temperature and the mixture was filtered through a Gelma Acrodisc. The filtrate was purified on Gilson LC using a Luna reverse phase column (10μ, C18, 250×21.2 mm) eluting with a gradient of 20-95% ACN/water (0.5% TFA). The desired fractions were combined and evaporated in vacuo. This residue was dissolved in TFA (3 mL) and allowed to stand at room temperature for 15 minutes and then the solvent was evaporated in vacuo to give a white solid. This solid was suspended in ACN (10 mL) and the solvent removed in vacuo to give the title compound. 1H NMR (DMSO-d6) δ=8.52 (d, 1H, J=3.8 Hz), 8.41 (s, 1H), 8.19 (d, 1H, J=7.9 Hz), 7.74 (s, 1H), 7.60 (s, 1H), 7.55 (s, 1H), 7.19 (dd, 1H, J=4 and 8.9 Hz) and 5.49 (s, 2H) ppm. HRMS (M+1): 445.9991.

Workup

  1. temperatureto cool to room temperature
  2. filtrationthe mixture was filtered through a Gelma Acrodisc
  3. customThe filtrate was purified on Gilson LC
  4. washeluting with a gradient of 20-95% ACN/water (0.5% TFA)
  5. customevaporated in vacuo
  6. dissolutionThis residue was dissolved in TFA (3 mL)
  7. customthe solvent was evaporated in vacuo
  8. customto give a white solid
  9. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-081f045b96e54b9aa9d7b8967cf45893
Source dataset
uspto-grants-2013_03
Patent number
US08404856B2

Reaction notes

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