Sodium Carbonate → HCID 66937124, compound

HRID 1963901Notes

Reaction equation

HRID 1963901 reaction equation
Br[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2([F:16])[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:5]=[CH:4][CH:3]=1.[Cl:17][C:18]1[C:19](B(O)O)=[CH:20][C:21]([F:24])=[N:22][CH:23]=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:17][C:18]1[C:19]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]([NH:8][CH2:9][C:10]3([F:16])[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[N:7]=2)=[CH:20][C:21]([F:24])=[N:22][CH:23]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 58284649HCID 58284649, compound

Product 1

HCID 66937124HCID 66937124, compound

Reagents, catalysts & solvents 4

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

Conditions

Temperature
100 °C

Procedure

A mixture of 6-bromo-N-((4-fluorotetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine (1 g, 3.46 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (1.092 g, 6.23 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.282 g, 0.346 mmol) in DME (13 mL) and 2M aqueous Na2CO3 (5.19 mL, 10.38 mmol) in a sealed tube was heated at 100° C. for 2 hr. The mixture was cooled to ambient temperature and was diluted with EtOAc (˜50 mL) and saturated aqueous NaHCO3. 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, 80 g, EtOAc/heptane= 5/95 for 4 min, then EtOAc/heptane= 5/95 to 50/50 over 18 min, then EtOAc/heptane= 50/50]providing 5′-chloro-2′-fluoro-N-((4-fluorotetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridin-6-amine as a colorless oil. Yield: 1.00 g. LCMS (m/z): 340.1 [M+H]+; Retention time=0.67 min.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. washThe separated organic layer was washed with saturated aqueous NaHCO3 (2×)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered off
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography [SiO2, 80 g, EtOAc/heptane= 5/95 for 4 min

Sources & evidence

ORD record
ord-d41d1827e239429f8f4522955faee4fb
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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