Acetic Acid → (S)-Methyl 2-(9-((1H-imidazol-2-yl)methyl)-4-chloro-8-oxo-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetate

HRID 1985461노트

반응식

HRID 1985461 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:13][C@@H:14]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[C:15]([O:17]C)=O)[C:5]([CH2:11]Cl)=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.Cl.Cl.[NH:26]1[CH:30]=[CH:29][N:28]=[C:27]1[CH2:31][NH2:32].C(N(CC)CC)C.C(O)(=O)C>C(#N)C.ClCCl>[NH:26]1[CH:30]=[CH:29][N:28]=[C:27]1[CH2:31][N:32]1[C:15](=[O:17])[C@H:14]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:13][C:4]2[CH:3]=[C:2]([Cl:1])[C:10]3[NH:9][N:8]=[CH:7][C:6]=3[C:5]=2[CH2:11]1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 124178631H-imidazol-2-ylmethanamine dihydrochlorideHCID 59731905(S)-Dimethyl 2-((7-chloro-4-(chloromethyl)-1H-indazol-5-yl)methyl)succinate

생성물 1

HCID 59731852(S)-Methyl 2-(9-((1H-imidazol-2-yl)methyl)-4-chloro-8-oxo-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetate수율 24%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매

실험 절차

(S)-Dimethyl 2-((7-chloro-4-(chloromethyl)-1H-indazol-5-yl)methyl)succinate (250 mg, 0.63 mmol) and (1H-imidazol-2-yl)methanamine dihydrochloride (170 mg, 1.0 mmol) were combined and suspended in acetonitrile (10 mL). Triethylamine (800 μL, 5.7 mmol) was added to the mixture. Reaction was warmed to reflux for 3 hours. Acetic acid (1.5 mL) was added to the mixture. Reaction was heated at reflux for 20 hours. Mixture was cooled to room temperature then diluted with dichloromethane. Mixture was extracted twice with water. Aqueous layer was concentrated in vacuo. Residue was purified by preparatory HPLC. Water was lyophilized off. Remaining residue was passed through a column of Dowex 1×4-200 ion exchange resin eluting methanol. Title compound was recovered as amber residue in 24% yield. MS m/e (M+H)+=388.1.

후처리

  1. customReaction
  2. temperaturewas warmed
  3. temperatureto reflux for 3 hours
  4. customReaction
  5. temperaturewas heated
  6. temperatureat reflux for 20 hours
  7. extractionMixture was extracted twice with water
  8. concentrationAqueous layer was concentrated in vacuo
  9. customResidue was purified by preparatory HPLC
  10. washeluting methanol
  11. customTitle compound was recovered as amber residue in 24% yield

출처 및 근거

ORD 기록
ord-ab20d704380448de88ba78a9afc8cc19
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07544680B2

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