1,2-Dichloroethane → 3-[5-Oxo-pyrrolidine-2(S)-carbonylamino]-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepine

HRID 609723ノート

反応式

HRID 609723 の反応式
Br.[NH2:2][CH:3]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]=2[NH:5][C:4]1=[O:20].[NH4+].[NH4+].[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[Ce+4].C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[K+].Br.C(O)(=O)C.[NH:65]1[C:69](=[O:70])[CH2:68][CH2:67][C@H:66]1[C:71](O)=[O:72].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(#N)C>[O:70]=[C:69]1[NH:65][C@H:66]([C:71]([NH:2][CH:3]2[N:9]=[C:8]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:7]3[CH:16]=[CH:17][CH:18]=[CH:19][C:6]=3[NH:5][C:4]2=[O:20])=[O:72])[CH2:67][CH2:68]1

参加物

10

反応物 7

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 180504Ceric ammonium nitrateHCID 6100505Dipotassium 2,3-dihydroxybutanedioateHCID 189176983-amino-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepine hydrogen bromideHCID 86754905HBr acetic acid (L)-pyroglutamic acid

生成物 1

HCID 229405853-[5-Oxo-pyrrolidine-2(S)-carbonylamino]-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepine

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6342Acetonitrile溶媒

実験手順

A solution of 3-amino-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepine hydrogen bromide (142 mg, 0.426 mmol), prepared by sequential treatment of an aqueous acetonitrile solution of the 4-methoxybenzyl derivative from example 5 with ammonium cerium IV nitrate, potassium tartrate solution and HBr/acetic acid-(L)-pyroglutamic acid (60.2 mg, 0.466 mmol), EDC (91 mg, 0.473 mmol), HOBT (63.5 mg, 0.473 mmol), and diisopropylethylamine (0.082 ml, 0.473 mmol) in DMF (5 ml) was stirred at room temperature for 18 hours. The resultant solution was concentrated in vacuo, and the residue partitioned between ethyl acetate and aqueous sodium bicarbonate solution. The organic extract was washed with brine, dried, (MgSO4), filtered, and concentrated. The residue was purified by preparative HPLC (C18, eluted with a 5:95 to 40:60 water:acetonitrile). Lyophilization provided the titled compound as a 1:1 mixture of diastereomers.

後処理

  1. concentrationThe resultant solution was concentrated in vacuo
  2. customthe residue partitioned between ethyl acetate and aqueous sodium bicarbonate solution
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried, (MgSO4),
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC (C18
  9. washeluted with a 5:95 to 40:60 water

出典と根拠

ORDレコード
ord-772ee2a01e944cc49e601f2e9601390d
出典データセット
uspto-grants-1999_12
特許番号
US05998407

反応ノート

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