Diisopropylethylamine → Allyl-O-({(14S)-1-azido-14-[(tert-butoxycarbonyl)amino]-13-oxo-3,6,9-trioxa-12-azahexadecan-16-yl}carbamoyl)-N-(tert-butoxycarbonyl)-L-tyrosinate

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1-Amino-11-azido-3,6,9-trioxaundecane	HCID 2735280	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	(2S)-4-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-amino}-2-[(tert-butoxycarbonyl)amino]butanoic acid	HCID 89544878	—
Solvent	Dichloromethane	HCID 6344	—
Product	Allyl-O-({(14S)-1-azido-14-[(tert-butoxycarbonyl)amino]-13-oxo-3,6,9-trioxa-12-azahexadecan-16-yl}carbamoyl)-N-(tert-butoxycarbonyl)-L-tyrosinate	HCID 89555031	—

Reaction Conditions

Temperature	60 °C

Reaction Steps

518 mg (0.92 mmol) of the compound from example 2A was dissolved in 15 ml dichloromethane. 200 mg (0.92 mmol) 2-{2-[2-(2-Azidoethoxy)ethoxy]ethoxy}ethanamine, 160 μl (0.92 mmol) N,N-diisopropylethylamine and 348 mg (0.92 mmol) HATU were added. The reaction mixture was heated for 30 min in a sealed tube at 60° C. in a microwave synthesizer. From the reaction mixture the solvent was removed under reduced pressure. The raw product was purified by preparative RP-HPLC on a C18 column with a water methanol gradient from 9/1 to 1/9. The product-containing fractions were combined and concentrated to dryness under reduced pressure. This gave 276 mg (0.34 mmol, 37% of theory) of the desired product.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09315543B2
Source dataset	uspto-grants-2016_04
ORD ID	ord-ebec0d5203f74f1eb3e0b48f20a1b6c8
Source note	uspto-grants-2016_04