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

HRID 380198Notes

Reaction equation

HRID 380198 reaction equation
[S:1]1[C:5]([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][N:13]([NH2:37])[CH2:14][C@H:15]([OH:36])[C@@H:16]([NH:24][C:25](=[O:35])[C@H:26]([CH:32]([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.[CH3:45][O:46][C:47]([NH:49][C@H:50]([C:55](O)=[O:56])[C@H:51]([CH2:53][CH3:54])[CH3:52])=[O:48].[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:37][C:55](=[O:56])[C@H:50]([C@H:51]([CH2:53][CH3:54])[CH3:52])[NH:49][C:47]([O:46][CH3:45])=[O:48])[CH2:14][C@H:15]([OH:36])[C@@H:16]([NH:24][C:25](=[O:35])[C@H:26]([CH:32]([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: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 107684261-[4-(Thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-valyl)amino-6-phenyl-2-azahexaneHCID 28378062L-Isoleucine, N-(methoxycarbonyl)-

Product 1

HCID 4679542,5,6,10,13-Pentaazatetradecanedioic acid, 8-hydroxy-12-(1-methylethyl)-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, 0.6 mmol of 1-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-valyl)amino-6-phenyl-2-azahexane and 198 μl (1.8 mmol) of NMM in 5.8 ml of DMF are added to 136 mg (0.72 nmol) of N-methoxycarbonyl-(L)-iso-leucine and 179 mg (0.60 mmol) of TPTU in 3 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: TLC: Rf=0.59 (methylene chloride/THF 3:1); HPLC20-100: tRet=14.0; FAB MS (M+H)+=697.

Sources & evidence

ORD record
ord-b5678574c0cb40cba3d8e74b53098107
Source dataset
uspto-grants-2001_10
Patent number
US06300519B1

Reaction notes

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