Dichloromethane → HCID 178434367, compound

HRID 1774970Notes

Reaction equation

HRID 1774970 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([CH3:11])=[N:9][N:8](C(OC(C)(C)C)=O)[C:5]2=[CH:6][N:7]=1.[CH3:19][N:20]1[CH:24]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH:22]=[N:21]1.C([O-])(=O)C.[K+].C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl.O.CN(C=O)C>[CH3:11][C:10]1[C:4]2[C:5](=[CH:6][N:7]=[C:2]([C:23]3[CH:22]=[N:21][N:20]([CH3:19])[CH:24]=3)[CH:3]=2)[NH:8][N:9]=1

Participants

10

Reactant 5

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 768508071,1-Dimethylethyl 5-bromo-3-methyl-1H-pyrazolo[3,4-c]pyridine-1-carboxylate

Product 1

HCID 178434367HCID 178434367, compoundYield 71.8%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

In a microwave vial was charged with tert-butyl 5-bromo-3-methyl-1H-pyrazolo[3,4-c]pyridine-1-carboxylate (53 mg, 0.17 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (70.6 mg, 0.34 mmol), potassium acetate (205.5 mg, 2.09 mmol), cesium carbonate (166.0 mg, 0.51 mmol), and bis(diphenylphosphino)ferrocene]dichloropalladium (II), complexed with dichloromethane (1:1) (13.9 mg, 0.017 mmol). DMF (2.6 mL) and water (0.5 mL) were added. Nitrogen was passed through the mixture for 15 minutes and the vial was capped. The reaction mixture was subjected to microwave irradiation at 125° C. for 20 min. The reaction mixture was filtered through a pad of Celite® and diluted with water and EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered, and evaporated in vacuo. The crude product was purified using flash chromatography (Si-PPC gradient elution, solvent: 50-100% ethyl acetate in heptanes, followed by 0-30% methanol in ethyl acetate) to give 127 as a foam (26.0 mg, 71.8%). 1H NMR (400 MHz, DMSO) δ 13.08 (broad s, 1H), 8.90 (s, 1H), 8.19 (s, 1H), 7.98 (s, 1H), 7.94 (s, 1H), 3.88 (s, 3H), 2.53 (s, 3H). LC/MS: m/z 214.1 [M+1]

Workup

  1. customthe vial was capped
  2. customirradiation at 125° C. for 20 min
  3. filtrationThe reaction mixture was filtered through a pad of Celite®
  4. additiondiluted with water and EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe crude product was purified
  10. washflash chromatography (Si-PPC gradient elution, solvent: 50-100% ethyl acetate in heptanes, followed by 0-30% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-d6782a0f496240aa933531552f8e0d2c
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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