BIIB-021

86604-75-3

10310-21-1

848695-25-0

The general procedure for the synthesis of 6-chloro-9-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]-9H-purin-2-amine (BIIB021) from 2-chloromethyl-3,5-dimethyl-4-methoxypyridine hydrochloride and 2-amino-6-chloropurine was as follows: 1. 2-Amino-6-chloropurine (10 mmol) and anhydrous potassium carbonate (12 mmol) were weighed separately and added to 25 mL of DMSO in a 50 mL round bottom flask. 2. The reaction mixture was heated to 48°C in an oil bath with continuous stirring for 30 minutes. 3. 2-chloromethyl-3,5-dimethyl-4-methoxypyridine hydrochloride (11 mmol) was weighed and added to the above reaction solution in 3 portions at 30 minute intervals. 4. After continuing the reaction at 48°C for 10 hours, the reaction temperature was adjusted to 22°C and stirred for 2 hours. 5. Upon completion of the reaction, the reaction mixture was filtered and the filtrate was retained. 6. A mixture of water and isopropanol (1:1 by volume) was added slowly and dropwise to the filtrate until the solution became turbid. 7. Place the turbid solution in a refrigerator overnight. 8. Collect the precipitate by filtration to obtain the target product BIIB021. The product 6-chloro-9-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]-9H-purin-2-amine (BIIB021) was a pale yellow solid with 77% yield.