Dichloromethane → 6-(5-chloro-2-fluoropyridin-4-yl)-5-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl) pyrazin-2-amine

HRID 1623388노트

반응식

HRID 1623388 반응식
Cl[C:2]1[N:3]=[CH:4][C:5]([NH:16][CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[N:6][C:7]=1[C:8]1[C:13]([Cl:14])=[CH:12][N:11]=[C:10]([F:15])[CH:9]=1.[C:24]([O-])([O-])=O.[Na+].[Na+].CB(O)O.C(Cl)Cl>COCCOC.CCOC(C)=O.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:14][C:13]1[C:8]([C:7]2[N:6]=[C:5]([NH:16][CH2:17][CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[CH:4]=[N:3][C:2]=2[CH3:24])=[CH:9][C:10]([F:15])=[N:11][CH:12]=1

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 139377Methylboronic AcidHCID 866506355-chloro-6-(5-chloro-2-fluoropyridin-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine

생성물 1

HCID 669368756-(5-chloro-2-fluoropyridin-4-yl)-5-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl) pyrazin-2-amine수율 75%

시약·촉매·용매 3

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

반응 조건

온도
105 °C

실험 절차

To a degassed suspension of 5-chloro-6-(5-chloro-2-fluoropyridin-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (10 mg, 0.028 mmol), Na2CO3 (0.036 ml, 2 M, 0.072 mmol) and methylboronic acid (5 mg, 0.084 mmol) in DME (1 ml) was added PdCl2(dppf).CH2Cl2 adduct (6 mg, 7.35 μmol). The reaction was capped and heated to 105° C. for 4 hr an oil bath. The reaction was diluted with EtOAc and washed with H2O, sat NaCl. The organic layer was dried Na2SO4, filtered and concentrated. The crude was purified by column chromatography on silica gel (50% EtOAc/Hexane) to yield 6-(5-chloro-2-fluoropyridin-4-yl)-5-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (7 mg, 0.021 mmol, 74.2% yield). LCMS (m/z): 337.2 (MH+), retention time=0.81 min.

후처리

  1. customThe reaction was capped
  2. washwashed with H2O
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude was purified by column chromatography on silica gel (50% EtOAc/Hexane)

출처 및 근거

ORD 기록
ord-ec73363d320e46d88d70ef91df727b61
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08778951B2

반응 노트

불러오는 중…