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 132180ノート

反応式

HRID 132180 の反応式
[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

参加物

7

反応物 4

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

生成物 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)acetate収率 24%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

実験手順

(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.

後処理

  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

出典と根拠

ORDレコード
ord-c3a56f4dc34b46b6a4285494cd30614e
出典データセット
uspto-grants-2008_06
特許番号
US07384930B2

反応ノート

読み込み中…