Dichloromethane → HCID 58127452, compound

HRID 1963814Notes

Reaction equation

HRID 1963814 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9]([NH:14][CH2:15][CH:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[N:8]=1)(=O)=O.[Cl:24][C:25]1[C:26](B(O)O)=[CH:27][C:28]([F:31])=[N:29][CH:30]=1.C(Cl)Cl.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]>[Cl:24][C:25]1[C:26]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[C:9]([NH:14][CH2:15][CH:16]3[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)[N:8]=2)=[CH:27][C:28]([F:31])=[N:29][CH:30]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 86650603HCID 86650603, compound

Product 1

HCID 58127452HCID 58127452, compound

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 5-fluoro-6-((tetrahydro-2H-pyran-4-yl)methyl)aminopyridin-2-yl trifluoromethanesulfonate (712 mg, 1.987 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (697 mg, 3.97 mmol), PdCl2(dppf).CH2Cl2 adduct (162 mg, 0.199 mmol) in DME (8 mL) and 2 M aqueous Na2CO3 solution (2.6 mL, 1.987 mmol) in a sealed tube was heated at 95° C. for 3 hr. The mixture was allowed to cool 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 (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 to 25/75 over 20 min] providing 5′-chloro-2′,5-difluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridin-6-amine as a white solid. Yield: 570 mg. LCMS (m/z): 340.1 [M+H]+; Retention time=0.99 min.

Workup

  1. washThe separated organic layer was washed with saturated aqueous NaHCO3 (2×)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered off
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by column chromatography [SiO2, 40 g, EtOAc/heptane=0/100 to 25/75 over 20 min]

Sources & evidence

ORD record
ord-3f606f961fa54de1b194aa22c8d00907
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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