Triethylamine → 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(4-fluorobenzyl)pyrimidine-5-formamide

In THF (10 mL) were dissolved 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-pyrimidine-5-carboxylic acid (150 mg, 0.40 mmol), 4-fluorobenzylamine (56 mg, 0.45 mmol) and triethylamine (101 mg, 1 mmol). The reaction mixture was cooled in an ice bath and HATU (266 mg, 0.70 mmol) was added. The reaction was conducted at ambient temperature for 18 h. The reaction mixture was concentrated, followed by addition of water and extraction with ethyl acetate. The organic phase was dried, concentrated, and purified by silica gel column chromatography (DCM/methanol=20/1) to give 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(4-fluorobenzyl)pyrimidine-5-formamide (30 mg, 16% yield).

1. temperatureThe reaction mixture was cooled in an ice bath
2. concentrationThe reaction mixture was concentrated
3. additionfollowed by addition of water and extraction with ethyl acetate
4. customThe organic phase was dried
5. concentrationconcentrated
6. custompurified by silica gel column chromatography (DCM/methanol=20/1)

ORD-Eintrag

ord-49c4942fc0e14e5a8e9b8e5a59d7e7d5

Quelldatensatz

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09359371B2