2-Amino-2-methyl-1-propanol → 6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-(2-hydroxy-1,1-dimethyl-ethyl)-nicotinamide

Participants

Role	Name	HCID	Charge
Reactant	2-Amino-2-methyl-1-propanol	HCID 11807	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	1-Hydroxybenzotriazole hydrate	HCID 2796029	—
Reactant	6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid	HCID 66718150	—
Solvent	Methanol	HCID 887	—
Solvent	Dichloromethane	HCID 6344	—
Solvent	Tetrahydrofuran	HCID 8028	—
Product	6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-(2-hydroxy-1,1-dimethyl-ethyl)-nicotinamide	HCID 46928665	66.4%

Reaction Steps

To a solution of 6-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid (200 mg, 0.58 mmol) in THF (6 mL) was added 1-hydroxybenzotriazole hydrate (90.8 mg, 0.58 mmol), N-ethyldiisopropylamine (254 μL, 1.45 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (114 mg, 0.58 mmol) and 2-amino-2-methyl-1-propanol (53.4 mg, 0.58 mmol). The reaction mixture was stirred overnight at room temperature. Chromatography (silica, dichloromethane:methanol=0:100 to 95:5) afforded the title compound (160 mg, 66%) as a colorless oil. MS: m/e=416.2 [M+H]+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08222246B2
Source dataset	uspto-grants-2012_07
ORD ID	ord-94b9b274fbc7404fb2f4975602619aac
Source note	uspto-grants-2012_07