Dimethylformamide → 1-[4-(Thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-N-(N-methoxycarbonyl-(L)-valyl)-amino-5(S)-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino-6-phenyl-2-azahexane

HRID 380193ノート

反応式

HRID 380193 の反応式
[S:1]1[C:5]([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][N:13](N)[CH2:14][C@H:15]([OH:37])[C@@H:16]([NH:24][C:25](=[O:36])[C@H:26]([C:32]([CH3:35])([CH3:34])[CH3:33])[NH:27][C:28]([O:30][CH3:31])=[O:29])[CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:8][CH:7]=2)=[CH:4][N:3]=[CH:2]1.CN1CC[O:43][CH2:42]C1.CO[NH:48][C@H:49]([C:55]([OH:57])=O)[CH:50]([CH3:54])[CH:51]=C=O.[B-](F)(F)(F)F.CN(C(ON1[C:76](=[O:77])C=CC=C1)=[N+](C)C)C.C[N:79](C=O)C>>[S:1]1[C:5]([C:6]2[CH:11]=[CH:10][C:9]([CH:12]([NH2:79])[N:13]([C:55](=[O:57])[C@H:49]([CH:50]([CH3:51])[CH3:54])[NH:48][C:42]([O:77][CH3:76])=[O:43])[CH2:14][C@H:15]([OH:37])[C@@H:16]([NH:24][C:25](=[O:36])[C@H:26]([C:32]([CH3:35])([CH3:34])[CH3:33])[NH:27][C:28]([O:30][CH3:31])=[O:29])[CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:8][CH:7]=2)=[CH:4][N:3]=[CH:2]1

参加物

6

反応物 5

HCID 6228Dimethylformamide2 回HCID 79724-MethylmorpholineHCID 2733204O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 107925271-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino-6-phenyl-2-azahexaneHCID 86757485N-methoxy-carbonyl-(L)-valine

生成物 1

HCID 867557181-[4-(Thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-N-(N-methoxycarbonyl-(L)-valyl)-amino-5(S)-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino-6-phenyl-2-azahexane

実験手順

Under an argon atmosphere, 344 mg of 1-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino-6-phenyl-2-azahexane and 191 μl (1.74 mmol) of NMM in 5.6 ml of DMF are added to 122 mg (0.696 mmol) of N-methoxy-carbonyl-(L)-valine and 173 mg (0.58 mmol) of TPTU in 2.9 ml of DMF and the mixture is stirred at room temperature for 16 hours. The reaction mixture is poured into ice-water, stirred for 30 min and filtered. Column chromatography of the residue (SiO2; methylene chloride/THF 4:1) and stirring in ether yield the title compound: m.p: 134-135° C.; HPLC20-100: tRet=14.0; FAB MS (M+H)+=697.

後処理

  1. stirringstirred for 30 min
  2. filtrationfiltered
  3. stirringColumn chromatography of the residue (SiO2; methylene chloride/THF 4:1) and stirring in ether

出典と根拠

ORDレコード
ord-862456766f504c6480c83ce04ce0547d
出典データセット
uspto-grants-2001_10
特許番号
US06300519B1

反応ノート

読み込み中…