Diisopropylethylamine → Allyl-N-(tert-butoxycarbonyl)-O-{[(4R,7S)-4-carbamoyl-13,13-dimethyl-6,11-dioxo-1,1,1-triphenyl-12-oxa-2-thia-5,10-diazatetradecan-7-yl]carbamoyl}-L-tyrosinate

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
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	(2R)-2-amino-3-((triphenylmethyl)sulfanyl)propanamide	HCID 44432703	—
Reactant	(2S)-2-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-amino}-4-[(tert-butoxycarbonyl)amino]butanoic acid	HCID 89544567	—
Solvent	Dichloromethane	HCID 6344	—
Product	Allyl-N-(tert-butoxycarbonyl)-O-{[(4R,7S)-4-carbamoyl-13,13-dimethyl-6,11-dioxo-1,1,1-triphenyl-12-oxa-2-thia-5,10-diazatetradecan-7-yl]carbamoyl}-L-tyrosinate	HCID 89555014	—

Reaction Conditions

Temperature	60 °C

Reaction Steps

3.00 g (5.30 mmol) of the compound from example 13A was dissolved in 120 ml dichloromethane. 1.92 g (5.30 mmol) S-Trityl-L-cysteinamide, 0.92 ml (5.30 mmol) N,N-diisopropylethylamine and 2.02 g (5.30 mmol) HATU were added. The reaction mixture was split into 6 portions. The portions were heated for 30 min in a sealed tube at 60° C. in a microwave synthesizer. From the combined reaction mixture the solvent was removed by rotary evaporation (approx. 40° C., approx. 200 mbar, approx. 30 min.). The raw product was dissolved in dichloromethane and chromatographed over approx. 800 ml silica gel. Solvents used were dichloromethane/ethyl acetate 2/1, dichloromethane/ethyl acetate 1/1. The product-containing fractions were combined and concentrated to dryness under reduced pressure. This gave 4.91 g (3.73 mmol, 70% of theory, 69% purity) 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-9f756acfa4a24affbe967cb0943a17a6
Source note	uspto-grants-2016_04