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*))-

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)-valyl)amino-6-phenyl-2-azahexane	HCID 10768426	—
Reactant	L-Isoleucine, N-(methoxycarbonyl)-	HCID 28378062	—
Solvent	Dimethylformamide	HCID 6228	—
Product	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*))-	HCID 467954	—

Reaction Steps

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.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US06300519B1
Source dataset	uspto-grants-2001_10
ORD ID	ord-b5678574c0cb40cba3d8e74b53098107
Source note	uspto-grants-2001_10