Example 8: Synthesis of N-(3-hydroxyphenethyl)-2,6-dimethylthieno[2,3-d]pyrimidin-4-amine (final compound 22). a) Preparation of 2-amino-5-methylthiophene-3-carboxamide; according to Scheme 5 Step 1: 2-amino-5-methylthiophene-3-carbonitrile (4.00 g, 28.9 mmol) was dissolved in concentrated sulphuric acid (38.8 ml), and the reaction was stirred for 20 hours at room temperature. Upon completion of the reaction, the mixture was slowly poured into ice water (250 g) and the pH was adjusted with concentrated sodium hydroxide solution to 7. Subsequently, the mixture was extracted with ethyl acetate, the organic layer was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (Flashmart Pack: 85g / 60-40um, eluent: ethyl acetate) to afford 2-amino-5-methyl-3-thiophenecarboxamide (3.10g, 69% yield) as a brown solid.
