Thionyl Chloride → 6-[Amino-(6-methyl-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-chloro-phenyl)-l H-quinolin-2-one

HRID 1017727노트

반응식

HRID 1017727 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:26]4[CH:27]=[N:28][C:29]([CH3:32])=[CH:30][CH:31]=4)([C:20]4[N:21]([CH3:25])[CH:22]=[N:23][CH:24]=4)O)[CH:16]=3)[N:11]=[C:10]([O:33]C)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.S(Cl)(Cl)=O.CO.C(Cl)(Cl)Cl.[NH4+:45].[OH-]>C1(C)C=CC=CC=1>[NH2:45][C:18]([C:26]1[CH:27]=[N:28][C:29]([CH3:32])=[CH:30][CH:31]=1)([C:20]1[N:21]([CH3:25])[CH:22]=[N:23][CH:24]=1)[C:15]1[CH:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10](=[O:33])[CH:9]=[C:8]2[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1

참가 물질

5

반응물 3

HCID 24386Thionyl ChlorideHCID 18404110[4-(3-chloro-phenyl)-2-methoxy-quinolin-6-yl]-(6-methyl-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methanolHCID 21873181Chloroform methanol ammonium hydroxide

생성물 1

HCID 184041116-[Amino-(6-methyl-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-chloro-phenyl)-l H-quinolin-2-one수율 46.4%

시약·촉매·용매 1

HCID 1140Toluene용매

반응 조건

온도
85 °C

실험 절차

To [4-(3-chloro-phenyl)-2-methoxy-quinolin-6-yl]-(6-methyl-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methanol (0.118 g, 0.251 mmol) in toluene (5 ml) under an atmosphere of dry N2 was added thionyl chloride (0.18 ml, 2.51 mmol) dropwise. The reaction mixture was heated at 85° C. for 15 hours. Solvent and the excess thionyl chloride were removed under reduced pressure. The crude chloride was taken up in toluene and concentrated under vacuum. The resulting solid was dissolved in THF (10 mL) and to this solution at −78° C. was bubbled ammonia gas (NH3) for 10 minutes. The reaction mixture was stirred at ambient temperature under an atmosphere of N2 for additional 1.5 hours. After removal of THF, the product mixture was partitioned between CHCl3 and water. The organic layer was washed, dried over MgSO4 and concentrated under vacuum to give a brown solid. This was chromatographed on silica gel with CHCl3 then MeOH—CHCl3—NH4OH (5:95:0.1 to 10:89:1) as eluents to afford the title compound of Example 14A as a white solid (53 mg, 0.116 mmol, 46.4% yield).

후처리

  1. customSolvent and the excess thionyl chloride were removed under reduced pressure
  2. concentrationconcentrated under vacuum
  3. dissolutionThe resulting solid was dissolved in THF (10 mL) and to this solution at −78° C.
  4. customwas bubbled ammonia gas (NH3) for 10 minutes
  5. customAfter removal of THF
  6. customthe product mixture was partitioned between CHCl3 and water
  7. washThe organic layer was washed
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under vacuum
  10. customto give a brown solid
  11. customThis was chromatographed on silica gel with CHCl3

출처 및 근거

ORD 기록
ord-266bc33fdd21479fafdb288ebee88ce7
출처 데이터셋
uspto-grants-2002_11
특허 번호
US06479513B2

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