Dichloromethane → HCID 71253650, compound

HRID 1774997Notes

Reaction equation

HRID 1774997 reaction equation
Cl[C:2]1[C:10]2[C:5](=[CH:6][N:7]=[C:8]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[CH:9]=2)[N:4]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)[N:3]=1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=1B1OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].C(=O)([O-])[O-].[Na+].[Na+].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.C(#N)C>[F:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=1[C:2]1[C:10]2[C:5](=[CH:6][N:7]=[C:8]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[CH:9]=2)[N:4]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)[N:3]=1

Participants

10

Reactant 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 706994982-(2-Fluoro-5-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 71254297HCID 71254297, compound

Product 1

HCID 71253650HCID 71253650, compoundYield 98.9%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

In a microwave vial was charged with 3-chloro-5-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (29.4 mg, 0.093 mmol), 2-(2-fluoro-5-methoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (35.0 mg, 0.139 mmol), potassium acetate (13.6 mg, 0.14 mmol), sodium carbonate (14.7 mg, 0.14 mmol), and bis(diphenylphosphino)ferrocene]dichloropalladium (II), complexed with dichloromethane (1:1) (7.5 mg, 9.2E−3 mmol). Degassed acetonitrile (0.8 mL) and water (0.3 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 25 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 concentrated under reduced pressure. The crude product was purified using flash chromatography (Si-PPC gradient elution, solvent: 10-100% ethyl acetate in heptanes) to give 3-(2-fluoro-5-methoxyphenyl)-5-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine as a foam (37.3 mg, 98.9%). 1H NMR (400 MHz, CDCl3) δ 9.12 (s, 1H), 7.95 (s, 1H), 7.90 (s, 1H), 7.81 (d, J=2.8 Hz, 1H), 7.32 (dd, J=5.5, 3.2 Hz, 1H), 7.15 (t, J=9.4 Hz, 1H), 6.97-6.89 (m, 1H), 5.86 (dd, J=8.7, 2.1 Hz, 1H), 4.07-3.98 (m, 1H), 3.93 (s, 3H), 3.86-3.74 (m, 4H), 2.64-2.47 (m, 1H), 2.16 (d, J=9.7 Hz, 2H), 1.83-1.66 (m, 3H). LC/MS: m/z 408.2 [M+1].

Workup

  1. customthe vial was capped
  2. customirradiation at 125° C. for 25 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. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified
  10. washflash chromatography (Si-PPC gradient elution, solvent: 10-100% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-e37bc9dd9259442b9464445be31536cd
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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