Dichloromethane → 5'-Chloro-2'-fluoro-N-[(oxan-4-yl)methyl][2,4'-bipyridin]-6-amine

HRID 1963808Notes

Reaction equation

HRID 1963808 reaction equation
Br[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:5]=[CH:4][CH:3]=1.[Cl:16][C:17]1[C:18](B(O)O)=[CH:19][C:20]([F:23])=[N:21][CH:22]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCOC(C)=O.CO.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:16][C:17]1[C:18]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]([NH:8][CH2:9][CH:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[N:7]=2)=[CH:19][C:20]([F:23])=[N:21][CH:22]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 58127218HCID 58127218, compound

Product 1

HCID 581271025'-Chloro-2'-fluoro-N-[(oxan-4-yl)methyl][2,4'-bipyridin]-6-amineYield 80.8%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 6-bromo-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine (C, 271 mg, 1 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (351 mg, 2.000 mmol), PdCl2(dppf).CH2Cl2 adduct (82 mg, 0.100 mmol) in DME (4.5 mL) and 2M Na2CO3 (318 mg, 3.00 mmol) was heated in a sealed tube at about 103° C. for about 2 hr. The mixture then was cooled to ambient temperature, diluted with EtOAc (˜25 mL) and MeOH (˜5 mL), filtered, and concentrated in vacuo to yield a resulting residue. The resulting residue was purified by column chromatography [SiO2, 12 g, EtOAc/heptane=10/90 to 50/50]. Fractions were combined and concentrated in vacuo providing 5′-chloro-2′-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridin-6-amine (260 mg) as a yellow thick oil. LCMS (m/z): 322.1/323.9 [M+H]+; Retention time=0.60 min.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated in vacuo
  3. customto yield a resulting residue
  4. customThe resulting residue was purified by column chromatography [SiO2, 12 g, EtOAc/heptane=10/90 to 50/50]
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-916693c092a54ab3a9b5483c6a32a603
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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