Diisopropylethylamine → (9H-Fluoren-9-yl)methyl(S)-1-((benzo[b]thiophen-3-ylmethyl)((S)-1,1-diethoxypropan-2-yl)amino)-1,4-dioxo-4-(tritylamino)butan-2-ylcarbamate

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Fmoc-Asn(Trt)-OH	HCID 640248	—
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	(S)-N-(benzo[b]thiophen-3-ylmethyl)-1,1-diethoxypropan-2-amine	HCID 67088371	—
Solvent	Water	HCID 962	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	(9H-Fluoren-9-yl)methyl(S)-1-((benzo[b]thiophen-3-ylmethyl)((S)-1,1-diethoxypropan-2-yl)amino)-1,4-dioxo-4-(tritylamino)butan-2-ylcarbamate	HCID 131730614	56.1%

Reaction Steps

According to the procedure described in the synthesis method of Compound III-1, (S)—N-(benzo[b]thiophen-3-ylmethyl)-1,1-diethoxypropan-2-amine (Compound IX-6) 13.2 g (45 mmol) and Fmoc-Asn(Trt)-OH 35.1 g (58.8 mmol) were dissolved in DMF (200 ml). HATU (25.6 g, 67.5 mmol) and DIEA (8.7 g, 67.5 mmol) were added at room temperature. The mixture was stirred overnight at room temperature. The mixture was poured into water (800 ml). The solution was extracted with EA (300 ml×3). The combined extracts were dried over Na2SO4 and then filtered. The solvent was removed in vacuo. The residue was purified by column chromatography on silica gel with PE:EA=30:1 to 5:1 to give the title compound 22.0 g, (yield 56%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08455488B2
Source dataset	uspto-grants-2013_06
ORD ID	ord-803e5354c83549338d1610418ffd5d69
Source note	uspto-grants-2013_06