ethyl 2-(thiazol-2-yl)pyrimidine-5-carboxylate synthesis

Yield:-

Reaction Conditions:

Stage #1: thiazole-2-carbonitrilewith N-Acetylcysteine;ammonium acetate in methanol;Heating / reflux;
Stage #2: C₆H₇O₄^(1-)*Na⁽¹⁺⁾ in N,N-dimethyl-formamide at 100; for 1.5 h;

Steps:

158.1; 158.2

Example 158; 2-Thiazol-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-methyl-indol-l-yl)-amide; Step 1 : A flask is charged with 2-cyanothiazole (6.7 g, 60.9 mmol), ammonium acetate (5.63 g, 73 mmol), N-acetylcysteine (993 mg, 6.09 mmol), and methanol (6OmL). The reaction is then heated to reflux overnight. The reaction is reduced in vacuo to yield a residue that is used in the next step without further modifications. Step 2: The crude residue from Step 1 is suspended in DMF (100 mL). To this is added sodium 2-ethoxycarbonyl-3-oxo-but-l-en-l-olate (13.86 g, 70 mmol). The reaction is then heated to 100⁰C for 1.5 h then allowed to cool to rt. The reaction is then poured into ice water (1 L). The suspension is filtered and the filtrate is successively extracted with DCM (100 mL) and EtOAc (200 mL). The organic layers are dried (Na₂SO₄), filtered and concentrated to yield a residue (10.31 g).

References:

WO2008/121670,2008,A1 Location in patent:Page/Page column 155-156