Sodium Carbonate → 3-(2-fluorophenyl)-5-(1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

HRID 1774975Notes

Reaction equation

HRID 1774975 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[F:17])=[N:9][N:8]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[C:5]2=[CH:6][N:7]=1.[NH:24]1[CH:28]=[C:27](B(O)O)[CH:26]=[N:25]1.C([O-])([O-])=O.[Na+].[Na+].COCCOC.CCO>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(OCC)(=O)C>[F:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:10]1[C:4]2[C:5](=[CH:6][N:7]=[C:2]([C:27]3[CH:28]=[N:24][NH:25][CH:26]=3)[CH:3]=2)[N:8]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[N:9]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 177502781H-Pyrazole-4-boronic acidHCID 20074477Dimethoxyethane ethanolHCID 866766855-bromo-3-(2-fluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

Product 1

HCID 712535923-(2-fluorophenyl)-5-(1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Procedure

A microwave tube charged with 5-bromo-3-(2-fluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (376 mg, 1 mmol), 1H-pyrazol-4-ylboronic acid (224 mg, 2 mmol), Pd(dppf)Cl2 (50 mg, 0.0625 mmol), saturated solution of Na2CO3 (0.5 mL), and DME/EtOH (5 mL/0.5 mL) was irradiated under microwave at 140° C. for 1 h. After cooling down, ethyl acetate was added. The mixture was washed with water twice (2×20 mL), dried over anhydrous Na2SO4 and concentrated to afford the crude product. The crude product was purified by silica-gel column chromatography eluting with 50% ethyl acetate in heptane to afford 3-(2-fluorophenyl)-5-(1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine as a white solid (300 mg, 82%, ESI MS m/z=364 (M+1) which was treated with HCl/dioxane (4 mL, 3 mol/L) and stirred for overnight. The crude product was received by filtration and washed with a little dioxane. It was further purified by prep-HPLC eluting with 5 to 95% CH3CN in aqueous 10 mmol NH4HCO3 solution to afford 136 as a white solid (180 mg, 72%). 1H NMR (400 MHz, DMSO) δ 9.02 (s, 1H), 8.16 (s, 2H), 8.02 (m, 1H), 7.87 (m, 1H), 7.54 (m, 1H), 7.38 (m, 2H). ESI MS m/z=280 (M+1)

Workup

  1. customwas irradiated under microwave at 140° C. for 1 h
  2. temperatureAfter cooling down
  3. washThe mixture was washed with water twice (2×20 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customto afford the crude product
  7. customThe crude product was purified by silica-gel column chromatography
  8. washeluting with 50% ethyl acetate in heptane

Sources & evidence

ORD record
ord-5fc689c07bbc48809aa04502a86a0a51
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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