Diisopropylethylamine → Allyl-O-({(3S)-4-{[(2R)-1-anilino-1-oxo-3-(tritylsulfanyl)propan-2-yl]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	N-Phenyl-S-trityl-L-cysteinamide	HCID 89544907	—
Solvent	Dichloromethane	HCID 6344	—
Product	Allyl-O-({(3S)-4-{[(2R)-1-anilino-1-oxo-3-(tritylsulfanyl)propan-2-yl]amino}-3-[(tert-butoxycarbonyl)amino]-4-oxobutyl}carbamoyl)-N-(tert-butoxycarbonyl)-L-tyrosinate	HCID 89555021	—

Reaction Steps

456 mg (0.68 mmol) of the compound from example 2A was dissolved in 8 ml dichloromethane. 300 mg (0.68 mmol) N-Phenyl-S-trityl-L-cysteinamide, 0.12 ml (0.68 mmol) N,N-diisopropylethylamine and 260 mg (0.68 mmol) HATU were added. The reaction mixture was stirred at room temperature for 4 h. 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 361 mg (0.37 mmol, 53% 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-dd3e5b8391a44370b980e53ef52653ba
Source note	uspto-grants-2016_04