Sodium Carbonate → HCID 66937086, compound

HRID 1623323Notes

Reaction equation

HRID 1623323 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9]([NH:14][CH2:15][C:16]2([CH3:22])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[N:8]=1)(=O)=O.[Cl:25][C:26]1[C:27](B(O)O)=[CH:28][C:29]([F:32])=[N:30][CH:31]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCOC(C)=O.C([O-])(O)=O.[Na+].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(Cl)Cl>[Cl:25][C:26]1[C:27]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[C:9]([NH:14][CH2:15][C:16]3([CH3:22])[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)[N:8]=2)=[CH:28][C:29]([F:32])=[N:30][CH:31]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 86650614HCID 86650614, compound

Product 1

HCID 66937086HCID 66937086, compound

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
102 °C

Procedure

A mixture of 5-fluoro-6-((4-methyltetrahydro-2H-pyran-4-yl)methyl)aminopyridin-2-yl trifluoromethanesulfonate (600 mg, 1.611 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (565 mg, 3.22 mmol), PdCl2(dppf)-CH2Cl2 adduct (132 mg, 0.161 mmol) in DME (8 mL) and 2M aqueous Na2CO3 (3 mL, 6.00 mmol) in a sealed tube was heated at 102° C. for 10 hr. The mixture was cooled to ambient temperature and was diluted with EtOAc (˜100 mL) and saturated aqueous NaHCO3 solution. The separated organic layer was washed with saturated aqueous NaHCO3 solution (2×), dried over Na2SO4, filtered off and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 40 g, EtOAc/heptane=0/100 for 3 min, EtOAc/heptane=0/100 to 30/70 over 17 min, then EtOAc/heptane=30/70] providing 5′-chloro-2′,5-difluoro-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridin-6-amine as a colorless oil. Yield: 490 mg. LCMS (m/z): 354.2 [M+H]+; Retention time=1.05 min.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. washThe separated organic layer was washed with saturated aqueous NaHCO3 solution (2×)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered off
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography [SiO2, 40 g, EtOAc/heptane=0/100 for 3 min

Sources & evidence

ORD record
ord-183fa66edad946cda479728a6273ccdd
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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