Acetic Acid → 1-butyl-3-(1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1,8-naphthyridin-2(1H)-one

Participants

Role	Name	HCID	Charge
Reactant	Acetic Acid	HCID 176	—
Reactant	Sodium hydride	HCID 24758	—
Reactant	2H-1,2,4-Benzothiadiazine-3-acetic acid ethyl ester 1,1-dioxide	HCID 658835	—
Reactant	1-butyl-2H-pyrido[2,3-d][1,3]oxazine-2,4(1H)-dione	HCID 10398542	—
Solvent	Hydrochloric Acid	HCID 313	—
Solvent	Tetrahydrofuran	HCID 8028	—
Product	1-butyl-3-(1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1,8-naphthyridin-2(1H)-one	HCID 135531244	33%

Reaction Conditions

Temperature	0 °C

Reaction Steps

To a solution of the product of Example 1B (0.220 g, 1.0 mmol) and the product of EXAMPLE 1C (0.268 g, 1.0 mmol) in anhydrous THF (10 mL) under nitrogen at 0° C. was added sodium hydride (95%, 0.10 g, 4.0 mmol). The reaction was heated to reflux for 3 hours, cooled to 0° C., and to it was added dropwise glacial acetic acid (2 mL). The resulting mixture was heated to reflux for 2 hours, cooled to ambient temperature, and diluted with aqueous hydrochloric acid (0.1 M, 10 mL). The resulting precipitate was collected by filtration, washed with water and diethyl ether and dried to give the title compound (0.130 g, 33%). MS (ESI−) m/z 397 (M−H)−.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07902203B2
Source dataset	uspto-grants-2011_03
ORD ID	ord-c395f635f38f47a995f26ed631b2d125
Source note	uspto-grants-2011_03