Diisopropylethylamine → Allyl-O-({(3S)-4-[(6-{[(2R)-1-amino-1-oxo-3-(tritylsulfanyl)propan-2-yl]amino}-6-oxohexyl)-amino]-3-[(tert-butoxycarbonyl)amino]-4-oxobutyl}carbamoyl)-N-(tert-butoxycarbonyl)-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	(2S)-4-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-amino}-2-[(tert-butoxycarbonyl)amino]butanoic acid	HCID 89544878	—
Reactant	6-Amino-N-[(2R)-1-amino-1-oxo-3-(tritylsulfanyl)propan-2-yl]hexanamide	HCID 89545090	—
Solvent	Dichloromethane	HCID 6344	—
Product	Allyl-O-({(3S)-4-[(6-{[(2R)-1-amino-1-oxo-3-(tritylsulfanyl)propan-2-yl]amino}-6-oxohexyl)-amino]-3-[(tert-butoxycarbonyl)amino]-4-oxobutyl}carbamoyl)-N-(tert-butoxycarbonyl)-L-tyrosinate	HCID 89554992	—

Reaction Conditions

Temperature	60 °C

Reaction Steps

457 mg (0.81 mmol) of the compound from example 2A was dissolved in 15 ml dichloromethane. 384 mg (0.81 mmol) of the compound from example 21A, 141 μl (0.81 mmol) N,N-diisopropylethylamine and 307 mg (0.81 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 in two portions 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 255 mg (0.22 mmol, 28% 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-d4dbac289dd94c5981b85fe1d49358bc
Source note	uspto-grants-2016_04