4-Methylmorpholine → HCID 49841101, compound

https://huagongshe.com/reaction/1968286

Participants

Role	Name	HCID	Charge
Reactant	4-Methylmorpholine	HCID 7972	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	1-Hydroxybenzotriazole hydrate	HCID 2796029	—
Reactant	Azetidine-3-carbonitrile hydrochloride	HCID 45072465	—
Reactant	Pyrrolo[4,3,2-de][2,6]naphthyridine-4(3H)-acetic acid, α-(1,1-dimethylethyl)-1,5-dihydro-3-oxo-, (αR)-	HCID 58293442	—
Solvent	Dimethylformamide	HCID 6228	—
Product	HCID 49841101	HCID 49841101	39%

Reaction Steps

(R)-3,3-Dimethyl-2-(3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoic acid (80 mg, 0.278 mmol), HOBt hydrate (51.2 mg, 0.334 mmol), and EDC hydrochloride (80 mg, 0.418 mmol) were combined in DMF (2 mL). Azetidine-3-carbonitrile hydrochloride (49.5 mg, 0.418 mmol) and 4-methylmorpholine (0.124 mL, 1.114 mmol) were added, and the reaction mixture was stirred at room temperature for 2 h. The product was purified by preparative HPLC (10-50% AcCN/H2O with 0.035% TFA), concentrated in vacuo, and purified by flash column chromatography (8% MeOH/DCM) to afford the title compound (38 mg, 39%). 1H NMR (500 MHz, CD3OD) δ 1.17 (s, 9H), 3.58-3.72 (m, 1H), 4.13-4.65 (m, 4H), 5.35-5.45 (m, 3H), 7.28-7.38 (m, 1H), 7.95 (d, J=15.5 Hz, 1H), 8.33-8.40 (m, 1H). [M+H] calc'd for C19H21N5O2, 352; found, 352.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08420816B2
Source dataset	uspto-grants-2013_04
ORD ID	ord-a053516da4c24016a78ffdfa02c637be
Source note	uspto-grants-2013_04