4-Methylmorpholine → 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

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	1-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino-6-phenyl-2-azahexane	HCID 10792527	—
Reactant	(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acid	HCID 10942966	—
Solvent	Dimethylformamide	HCID 6228	—
Product	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	HCID 86755718	—

Reaction Steps

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.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US06166004
Source dataset	uspto-grants-2000_12
ORD ID	ord-5fd8fe4711644a0c91a42d99f88e2749
Source note	uspto-grants-2000_12