BIIB-021 synthesis
- Product Name:BIIB-021
- CAS Number:848695-25-0
- Molecular formula:C14H15ClN6O
- Molecular Weight:318.76
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.
86604-75-3
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10310-21-1
556 suppliers
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848695-25-0
141 suppliers
$39.00/1mg
Yield:848695-25-0 77%
Reaction Conditions:
Stage #1: 2-amino-6-chloropurinewith potassium carbonate in dimethyl sulfoxide at 48; for 0.5 h;
Stage #2: 2-(chloromethyl)-4-methoxy-3,5-dimethylpyridine hydrochloride in dimethyl sulfoxide at 22 - 48; for 12.5 h;
Steps:
1 1. Synthesis of parent drug
Weigh respectively 2-amino-6-chloropurine 10mmol, anhydrous potassium carbonate 12mmol, the amount of 25mL DMSO was added to a 50mL round bottom flask, the oil bath was heated to 48 ° C, stirring reaction 30min;11 mmol of 2-chloromethyl-3,5-dimethylpyridine hydrochloride was weighed and added to the above reaction solution in 3 portions at intervals of 30 minutes.After reacting at 48 °C for 10 h, the temperature was set to 22 °C and stirred for 2 h. After the reaction was completed, the reaction solution was filtered and the filtrate was retained.The volume ratio of water: isopropyl alcohol = 1:1 mixed solution was added to the filtrate, until the solution became turbid to stop dropping, and the solution was placed in a refrigerator to stand still overnight. The filter residue was parent molecule BIIB021. 6-Chloro-9-[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]-9H-purin-2-amine (BIIB021):Light yellow solid; Yield: 77%;
References:
CN107857763,2018,A Location in patent:Paragraph 0014-0016
86604-75-3
564 suppliers
$10.00/1g
10310-21-1
556 suppliers
$10.00/5g
848695-25-0
141 suppliers
$39.00/1mg