Potassium Fluoride → Tert-butyl (6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl)carbamate

HRID 1253554Notes

Reaction equation

HRID 1253554 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:10]2[N:11]([N:13]=[CH:14][CH:15]=2)[CH:12]=1)(=O)=O.[CH3:26][N:27]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[N:28]1.[F-].[K+].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>CN(C=O)C.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]>[CH3:26][N:27]1[CH:31]=[C:30]([C:7]2[CH:8]=[C:9]([NH:16][C:17](=[O:18])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C:10]3[N:11]([N:13]=[CH:14][CH:15]=3)[CH:12]=2)[CH:29]=[N:28]1

Participants

7

Reactant 4

HCID 522689Potassium FluorideHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 866570564-[(Tert-butoxycarbonyl)amino]pyrazolo[1,5-a]pyridin-6-yl trifluoromethanesulfonate

Product 1

HCID 58404864Tert-butyl (6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl)carbamate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

4-[(tert-butoxycarbonyl)amino]pyrazolo[1,5-a]pyridin-6-yl trifluoromethanesulfonate (20.0 mg, 0.052 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (21.8 mg, 0.105 mmol), tris(dibenzylideneacetone)dipalladium (0) (4.8 mg, 5.2 μmol), potassium fluoride (10.1 mg, 0.173 mmol), and tri-tert-butylphosphonium tetrafluoroborate (3.0 mg, 10.0 μmol) were suspended in DMF. The mixture was sparged with argon for 10 minutes, then heated to 100° C. for 2 h. The reaction mixture was 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 column chromatography on silica gel (methanol/ethyl acetate gradient) to afford a yellow gum. The gum 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 afford tert-butyl [6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]carbamate. 1H NMR (500 MHz, CDCl3) δ 8.35 (s, 1H); 7.89 (s, 2H); 7.76 (s, 1H); 7.66 (s, 1H); 6.73 (s, 1H); 6.47 (s, 1H); 3.94 (s, 3H), 1.56 (s, 9H). LRMS (ESI) calculated for C16H20N5O2 [M+H]+, 314.2; found 314.1.

Workup

  1. customThe mixture was sparged with argon for 10 minutes
  2. additionThe reaction mixture was diluted in ethyl acetate
  3. washwashed with saturated aqueous sodium hydrogen carbonate and brine
  4. dry with materialthen dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (methanol/ethyl acetate gradient)
  8. customto afford a yellow gum
  9. customThe gum was purified by preparative HPLC Reverse phase (C-18)
  10. washeluting with Acetonitrile/Water+0.05% TFA
  11. additionThe fractions containing product
  12. additiondiluted in ethyl acetate
  13. washwashed with aqueous sodium bicarbonate
  14. dry with materialdried over sodium sulfate
  15. filtrationThe solution was filtered
  16. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f3fb59e3b67341bc835cf6070d9806a2
Source dataset
uspto-grants-2013_06
Patent number
US08455477B2

Reaction notes

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