Example 7: Preparation of 4-(4-amino-6-chloropyrimidin-2-ylamino)benzonitrile (Compound Ia)
To a solution of 4-aminobenzonitrile (ABN; 7 g; 59.3 mmol) in 2-butanol (190 ml) was slowly added 2,6-dichloropyrimidin-4-amine (DCAP; 10.2 g; 62.2 mmol) at room temperature. The resulting suspension was heated to reflux (102 °C) and stirred continuously for 20 hours. Upon completion of the reaction, the suspension was cooled to 20-25 °C and stirring was continued for 1 h at this temperature. The solid product was separated by filtration, washed with 2-butanol (20 ml) and subsequently dried at 50 °C for 2 h at 10 mbar. The final product was 12.20 g of 4-(4-amino-6-chloropyrimidin-2-ylamino)benzonitrile hydrochloride in 73.0% yield. The purity of the product was analyzed by HPLC/MS as 99.0 area%.
