4-Methylmorpholine → 2,5,6,10,13-Pentaazatetradecanedioic acid, 12-(1,1-dimethylethyl)-8-hydroxy-3-(1-methylethyl)-4,11-dioxo-9-(phenylmethyl)-6-((4-(5-thiazolyl)phenyl)methyl)-, dimethyl ester, (3S,8S,9S,12S)-

HRID 1458437Notes

Reaction equation

HRID 1458437 reaction equation
[S:1]1[C:5]([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][N:13]([NH2:38])[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.CN1CCOCC1.[CH3:46][O:47][C:48]([NH:50][C@H:51]([C:55](O)=[O:56])[CH:52]([CH3:54])[CH3:53])=[O:49].[B-](F)(F)(F)F.CN(C(ON1C(=O)C=CC=C1)=[N+](C)C)C>CN(C=O)C>[S:1]1[C:5]([C:6]2[CH:7]=[CH:8][C:9]([CH2:12][N:13]([NH:38][C:55](=[O:56])[C@H:51]([CH:52]([CH3:53])[CH3:54])[NH:50][C:48]([O:47][CH3:46])=[O:49])[CH2:14][C@H:15]([OH:37])[C@@H:16]([NH:24][C:25](=[O:36])[C@H:26]([C:32]([CH3:34])([CH3:35])[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:10][CH:11]=2)=[CH:4][N:3]=[CH:2]1

Participants

6

Reactant 4

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 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acid

Product 1

HCID 4679522,5,6,10,13-Pentaazatetradecanedioic acid, 12-(1,1-dimethylethyl)-8-hydroxy-3-(1-methylethyl)-4,11-dioxo-9-(phenylmethyl)-6-((4-(5-thiazolyl)phenyl)methyl)-, dimethyl ester, (3S,8S,9S,12S)-

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

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-methoxycarbonyl-(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-8590eb1418614da9bbbfe7bdb3f9f7b6
Source dataset
uspto-grants-1998_12
Patent number
US05849911

Reaction notes

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