1-Hydroxybenzotriazole → methyl-[(S)-1-((S)-3-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-ylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester

Participants

Role	Name	HCID	Charge
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 2733084	—
Reactant	(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acid	HCID 7009590	—
Reactant	HCID 90037368	HCID 90037368	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	methyl-[(S)-1-((S)-3-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-ylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester	HCID 90037667	103.3%

Reaction Steps

A mixture of (S)-3-amino-8-methyl-2,3-dihydrobenzo[b][1,4]oxazepin-4(5H)-one trifluoroacetate (1.60 g, 5.23 mmol, Eq: 1.00), (S)-2-(tert-butoxycarbonyl(methyl)amino)propanoic acid (1.06 g, 5.23 mmol, Eq: 1.00), HOBT (801 mg, 5.23 mmol, Eq: 1.00), HBTU (1.98 g, 5.23 mmol, Eq: 1.00) at 0° C. and DIEA (2.03 g, 2.73 mL, 15.7 mmol, Eq: 3.00) in DMF (50 mL) was stirred at 0° C. for 1 h, diluted with EtOAc, washed with water, brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography to afford methyl-[(S)-1-((S)-3-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-ylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester (2.04 g) which was used without purification.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09394263B2
Source dataset	uspto-grants-2016_07
ORD ID	ord-78f742bb0b4d477a88e9d3359f49cb45
Source note	uspto-grants-2016_07