Dichloromethane → 3,5,5'-trichloro-2'-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4'-bipyridin-6-amine

참여 물질

역할	이름	HCID	투입량
반응물	Dichloromethane	HCID 6344	—
반응물	Sodium Carbonate	HCID 10340	—
반응물	(5-Chloro-2-fluoropyridin-4-yl)boronic acid	HCID 44754822	—
반응물	HCID 58284750	HCID 58284750	—
촉매	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
용매	1,2-Dimethoxyethane	HCID 8071	—
용매	Ethyl Acetate	HCID 8857	—
용매	Sodium Bicarbonate	HCID 516892	—
생성물	3,5,5'-trichloro-2'-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4'-bipyridin-6-amine	HCID 66937015	—

반응 단계

A mixture of 6-bromo-3,5-dichloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine (1 g, 2.94 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (0.774 g, 4.41 mmol), PdCl2(dppf).CH2Cl2 adduct (0.240 g, 0.294 mmol) in DME (12 mL) and 2M aqueous Na2CO3 solution (4 mL, 2.94 mmol) in a sealed tube was heated at 90° C. for 2 hr. The mixture was allowed to cool to ambient temperature and was diluted with EtOAc (˜100 mL) and saturated aqueous NaHCO3. The separated organic layer was washed with saturated aqueous NaHCO3 (2×), brine, dried over Na2SO4, filtered off and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 80 g, EtOAc/heptane=0/100 to 30/70 over 25 min] providing 3,5,5′-trichloro-2′-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridin-6-amine as a colorless liquid. Yield: 510 mg. LCMS (m/z): 391.9 [M+H]+; Retention time=1.14 min.

출처 및 근거

DOI	10.6084/m9.figshare.5104873.v1
특허 번호	US08778951B2
출처 데이터셋	uspto-grants-2014_07
ORD ID	ord-e4523a92dcda4f5da95a58488934794f
출처 메모	uspto-grants-2014_07