1-Hydroxybenzotriazole → Tert-butyl N-[1-[[(4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl]carbamoyl]cyclopropyl]carbamate

https://huagongshe.com/reaction/2068555

Participants

Role	Name	HCID	Charge
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1-((tert-Butoxycarbonyl)amino)cyclopropanecarboxylic acid	HCID 688396	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	(R)-5,6-Dihydro-4H-benzo[F]imidazo[1,2-A]azepin-4-amine	HCID 58304055	—
Solvent	Tetrahydrofuran	HCID 8028	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	Tert-butyl N-[1-[[(4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl]carbamoyl]cyclopropyl]carbamate	HCID 67234396	79%

Reaction Steps

Combine (4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-amine (570 mg, 2.86 mmol), 1-(tert-butoxycarbonylamino)cyclopropanecarboxylic acid (commercially available, 633.19 mg, 3.15 mmol), 1-hydroxybenzotriazole (464 mg, 3.43 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (658 mg; 3.43 mmol) in tetrahydrofuran (10 mL). Add diisopropylethylamine (599 μL, 3.43 mmol) and stir the reaction for approximately 16 hours at ambient temperature under nitrogen. Dilute the reaction with ethyl acetate, wash with dilute sodium bicarbonate and brine, dry over sodium sulfate, and concentrate the organic layer under reduced pressure. Purify the residue by flash chromatography (25% EtOAc/hexanes to 85% EtOAc/hexanes) to give the title compound (860 mg, 79%) as a white solid: MS (m/z): 383 (M+1).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08299061B2
Source dataset	uspto-grants-2012_10
ORD ID	ord-f81b889126af49dda6873b0babf6a856
Source note	uspto-grants-2012_10