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

HRID 1963890노트

반응식

HRID 1963890 반응식
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)[C:5]([Cl:16])=[CH:4][C:3]=1[Cl:17].[Cl:18][C:19]1[C:20](B(O)O)=[CH:21][C:22]([F:25])=[N:23][CH:24]=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:17][C:3]1[C:2]([C:20]2[C:19]([Cl:18])=[CH:24][N:23]=[C:22]([F:25])[CH:21]=2)=[N:7][C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[C:5]([Cl:16])[CH:4]=1

참가 물질

9

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 58284750HCID 58284750, 화합물

생성물 1

HCID 669370153,5,5'-trichloro-2'-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4'-bipyridin-6-amine

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매HCID 516892Sodium Bicarbonate용매

실험 절차

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.

후처리

  1. washThe separated organic layer was washed with saturated aqueous NaHCO3 (2×), brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered off
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by column chromatography [SiO2, 80 g, EtOAc/heptane= 0/100 to 30/70 over 25 min]

출처 및 근거

ORD 기록
ord-3e09a84183814f939dbd8568ed94322d
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415381B2

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