Synthesis of 2-Cyanopyrimidines

• Main Authors: Andreas S. Kalogirou, Panayiotis A. Koutentis
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: Molbank
• Subjects: heterocycle; pyrimidine; nucleophilic displacement; chlorination
• Online Access: https://www.mdpi.com/1422-8599/2019/4/M1086

4,6-Dichloro-2-(methylthio)pyrimidine (<b>7</b>) was converted to 4-chloro-6-methoxy-2-(methylthio)pyrimidine (<b>15</b>) and 4,6-dimethoxy-2-(methylthio)pyrimidine (<b>14</b>). Chlorination of the latter with <i>N</i>-chlorosuccinimide (NCS) affords 5-chloro-4,6-dimethoxy-2-(methylthio)pyrimidine (<b>16</b>) in 56% yield. Both methylthiopyrimidines <b>15</b> and <b>14</b> were converted in two steps to 4-chloro-6-methoxypyrimidine-2-carbonitrile (<b>13</b>) and 4,6-dimethoxypyrimidine-2-carbonitrile (<b>12</b>), respectively, after oxidation to sulfones and displacement of the sulfinate group with KCN. 4,6-Dimethoxypyrimidine-2-carbonitrile (<b>12</b>) was chlorinated with NCS to give 5-chloro-4,6-dimethoxypyrimidine-2-carbonitrile (<b>10</b>) in 53% yield. All new compounds were fully characterized.