Potassium Carbonate → HCID 178509955, compound

HRID 1952384Notes

Reaction equation

HRID 1952384 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:12]([OH:18])=[N:13][CH:14]=[CH:15][C:16]=2[Cl:17])[CH:9]=1)[C:5]#[N:6].Br[CH2:20][C:21]1[C:29]2[C:24](=[N:25][CH:26]=[CH:27][CH:28]=2)[N:23](C(OC(C)(C)C)=O)[N:22]=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:18])[N:13]([CH2:20][C:21]3[C:29]4[C:24](=[N:25][CH:26]=[CH:27][CH:28]=4)[NH:23][N:22]=3)[CH:14]=[CH:15][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 178509954HCID 178509954, compound

Product 1

HCID 178509955HCID 178509955, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 3-chloro-5-[(4-chloro-2-hydroxypyridin-3-yl)oxy]benzonitrile (150 mg, 0.534 mmol) in DMF (3 mL) was added tert-butyl 3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylate (167 mg, 0.534 mmol) and potassium carbonate (73.8 mg, 0.534 mmol) and the mixture warmed to 55° C. for 60 minutes. After this time, the reaction mixture was purified by preparative HPLC using a Luna reverse phase column (10μ, C18, 250×21.2 mm) and eluting with a gradient of 5-95% ACN/water (0.5% TFA). The desired fractions were combined and the solvent evaporated in vacuo. The residue was dissolved in TFA (10 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 evaporated in vacuo to give the title compound. 1H NMR (DMSO-d6) δ=13.64 (s, 1H), 8.52 (dd, 1H, J=1.6 and 4.5 Hz), 8.15 (dd, 1H, J=1.4 and 8.06 Hz), 7.90 (d, 1H, J=7.5 Hz), 7.73 (dd, 1H, J=1.7 and 1.4 Hz), 7.50 (dd, 1H, J=2.5 and 1.2 Hz), 7.41 (dd, 1H, J=3.2 and 1.9 Hz), 7.18 (dd, 1H, J=4.5 and 8.06 Hz), 6.61 (d, 1H, J=7.5 Hz) and 5.48 (s, 2H) ppm. HRMS (M+1): 412.0372.

Workup

  1. customAfter this time, the reaction mixture was purified by preparative HPLC
  2. washeluting with a gradient of 5-95% ACN/water (0.5% TFA)
  3. customthe solvent evaporated in vacuo
  4. dissolutionThe residue was dissolved in TFA (10 mL)
  5. customthe solvent was evaporated in vacuo
  6. customto give a white solid
  7. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-2e0b0f0d12294b9586be333106d330bb
Source dataset
uspto-grants-2013_03
Patent number
US08404856B2

Reaction notes

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