4-Methylmorpholine → 2,5,6,10,13-Pentaazatetradecanedioic acid, 8-hydroxy-3-(1-methylethyl)-12-(1-methylpropyl)-4,11-dioxo-9-(phenylmethyl)-6-((4-(2-thiazolyl)phenyl)methyl)-, 1-ethyl 14-methyl ester, (3S-(3R,8R,9R,12R(R*)))-

Participants

Role	Name	HCID	Charge
Reactant	4-Methylmorpholine	HCID 7972	—
Reactant	O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium Tetrafluoroborate	HCID 2733204	—
Reactant	N-Carbethoxy-L-valine	HCID 13221302	—
Reactant	HCID 66578170	HCID 66578170	—
Solvent	Dimethylformamide	HCID 6228	—
Product	2,5,6,10,13-Pentaazatetradecanedioic acid, 8-hydroxy-3-(1-methylethyl)-12-(1-methylpropyl)-4,11-dioxo-9-(phenylmethyl)-6-((4-(2-thiazolyl)phenyl)methyl)-, 1-ethyl 14-methyl ester, (3S-(3R,8R,9R,12R(R*)))-	HCID 467967	—

Reaction Steps

Under an argon atmosphere, 321 mg (0.60 mmol) of 1-[4-(thiazol-2-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-iso-leucyl)amino-6-phenyl-2-azahexane (Example 21b) and 182 mg (1.8 mmol) of NMM in 5.8 ml of DMF are added to 136 mg (0.72 mmol) of N-ethoxycarbonyl-(L)-valine and 178 mg (0.60 mmol) of TPTU in 3 ml of DMF and the mixture is stirred at room temperature for 15 hours. The reaction mixture is poured into ice-water, stirred for 30 min and filtered. Crystallisation from THF with DIPE and hexane yields the title compound: m.p.: 209-211 ° C.; HPLC20-100: tRet =15.2; FAB MS (M+H)+ =711.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US06166004
Source dataset	uspto-grants-2000_12
ORD ID	ord-ff1337124c6c457196cf061801c3fa04
Source note	uspto-grants-2000_12