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

HRID 1276970Notes

Reaction equation

HRID 1276970 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:56](O)=[O:57])[C@H:52]([CH2:54][CH3:55])[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:56](=[O:57])[C@H:51]([C@H:52]([CH2:54][CH3:55])[CH3:53])[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 28378062L-Isoleucine, N-(methoxycarbonyl)-

Product 1

HCID 4679492,5,6,10,13-Pentaazatetradecanedioic acid, 12-(1,1-dimethylethyl)-8-hydroxy-3-(1-methylpropyl)-4,11-dioxo-9-(phenylmethyl)-6-((4-(5-thiazolyl)phenyl)methyl)-, dimethyl ester, (3S-(3R*(R*),8R*,9R*,12R*))-

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Under an argon atmosphere, 292 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 (Example 2d) and 165 μl (1.5 mmol) of NMM in 4.8 ml of DMF are added to 113 mg of N-methoxycarbonyl-(L)-iso-leucine and 149 mg (0.50 mmol) of TPTU in 2.5 ml of DMF, and the mixture is stirred at room temperature for 14 hours and worked up analogously to Example 3, yielding the title compound: m.p: 139-141° C.; TLC: Rf =0.7 (methylene chloride/methanol 10:1); HPLC20-100 : tRet =14.6; FAB MS (M+H)+ =711.

Sources & evidence

ORD record
ord-506d1875478f4554aeb6e2643f07c548
Source dataset
uspto-grants-2000_12
Patent number
US06166004

Reaction notes

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