Water → HCID 58404803, compound

HRID 1253465Notes

Reaction equation

HRID 1253465 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:16][CH3:17])[C:5]2[N:6]([N:8]=[CH:9][C:10]=2[C:11]#[C:12][CH:13]2[CH2:15][CH2:14]2)[CH:7]=1.[CH3:18][N:19]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:20]1.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:13]1([C:12]#[C:11][C:10]2[CH:9]=[N:8][N:6]3[CH:7]=[C:2]([C:22]4[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=4)[CH:3]=[C:4]([O:16][CH3:17])[C:5]=23)[CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58404692HCID 58404692, compound

Product 1

HCID 58404803HCID 58404803, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

6-bromo-3-(cyclopropylethynyl)-4-methoxypyrazolo[1,5-a]pyridine (10.0 mg, 0.034 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (21.4 mg, 0.103 mmol), tetrakis(triphenylphosphine)palladium (0) (4.0 mg, 3.4 mmol), sodium carbonate (10.9 mg, 0.103 mmol) was suspended in 1,4-dioxane (900 μl/Water (100 μl). The mixture was sparged with Ar for 10 minutes, then heated to 90° C. for 4 h. The reaction mixture was cooled to ambient temperature, diluted in ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water+0.05% TFA. The fractions containing product were combined and diluted in ethyl acetate, then washed with aqueous sodium bicarbonate and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure to give 3-(cyclopropylethynyl)-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine. 1H NMR (600 MHz, CDCl3) δ 8.16 (s, 1H); 7.86 (s, 1H); 7.71 (s, 1H); 7.59 (s, 1H); 6.46 (s, 1H); 3.98 (s, 3H); 3.95 (s, 3H); 1.43-1.46 (m, 1H); 0.78-0.89 (m, 4H). LRMS (ESI) calculated for C17H17N4O [M+H]+, 293.1; found 293.1.

Workup

  1. customThe mixture was sparged with Ar for 10 minutes
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. additiondiluted in ethyl acetate
  4. washwashed with saturated aqueous sodium hydrogen carbonate and brine
  5. dry with materialthen dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC Reverse phase (C-18)
  9. washeluting with Acetonitrile/Water+0.05% TFA
  10. additionThe fractions containing product
  11. additiondiluted in ethyl acetate
  12. washwashed with aqueous sodium bicarbonate
  13. dry with materialdried over sodium sulfate
  14. filtrationThe solution was filtered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9c037f7479a1449db08b97784adc2c3a
Source dataset
uspto-grants-2013_06
Patent number
US08455477B2

Reaction notes

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