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 380193Notes

Reaction equation

HRID 380193 reaction equation
[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

Participants

6

Reactant 5

HCID 6228Dimethylformamide2×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

Product 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

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-862456766f504c6480c83ce04ce0547d
Source dataset
uspto-grants-2001_10
Patent number
US06300519B1

Reaction notes

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