2,4-Dichloro-5-fluoropyrimidine → 2-chloro-5-fluoro-N4-[4-(prop-2-ynyloxy)phenyl]-4-pyrimidineamine

HRID 1725695

반응식

HRID 1725695 반응식
[CH2:1]([O:4][C:5]1[CH:11]=[CH:10][C:8]([NH2:9])=[CH:7][CH:6]=1)[C:2]#[CH:3].[Cl:12][C:13]1[N:18]=[C:17](Cl)[C:16]([F:20])=[CH:15][N:14]=1>CO.O.CCOC(C)=O>[Cl:12][C:13]1[N:18]=[C:17]([NH:9][C:8]2[CH:10]=[CH:11][C:5]([O:4][CH2:1][C:2]#[CH:3])=[CH:6][CH:7]=2)[C:16]([F:20])=[CH:15][N:14]=1

참가 물질

5

반응물 2

HCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 126688624-(Prop-2-yn-1-yloxy)aniline

생성물 1

HCID 575628992-chloro-5-fluoro-N4-[4-(prop-2-ynyloxy)phenyl]-4-pyrimidineamine수율 243.6%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 22242641Methanol--water (1/1)용매

실험 절차

Crude 4-(prop-2-ynyloxy)aniline (0.750 g, 5.10 mmol) and 2,4-dichloro-5-fluoropyrimidine (1.27 g, 0.760 mmol) were stirred in MeOH/water (4:1, 35 mL) at room temperature for 18 h. The reaction mixture was diluted with EtOAc (200 mL) and washed with 1N HCl (50 mL) and brine (50 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexanes ramped to EtOAc:hexanes (1:10)) to provide 2-chloro-5-fluoro-N4-[4-(prop-2-ynyloxy)phenyl]-4-pyrimidineamine as a light brown solid (0.514 g). 1H NMR (CDCl3): δ 8.03 (d, J=2.7 Hz, 1H), 7.53 (d, J=8.7 Hz, 2H), 7.02 (d, J=8.7 Hz, 2H), 6.86 (s, 1H), 4.71 (d, J=2.4 Hz, 2H), 2.55 (t, J=2.4 Hz, 1H); LCMS: purity: 99%; MS (m/e): 279 (MH+).

후처리

  1. washwashed with 1N HCl (50 mL) and brine (50 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (silica gel, hexanes ramped to EtOAc:hexanes (1:10))

출처 및 근거

ORD 기록
ord-e54284acc95f4d05997c14a84c603153
출처 데이터셋
uspto-grants-2009_02
특허 번호
US07491732B2

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