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ChemicalBook CAS DataBase List Minoxidil

Minoxidil synthesis

3synthesis methods
Minoxidil, 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine (22.8.5), is synthesized from barbituric acid, the reaction of which with phosphorous oxychloride gives 2,4,6-trichloropyrimidine (22.8.1). Upon reaction with ammonium, this turns into 2,4-diamino-6-chloropyrimidine (22.8.2). Next, the resulting 2,4-diamino-6- chloropyrimidine (22.8.2) undergoes reaction with 2,4-dichlorophenol in the presence of potassium hydroxide, giving 2,4-diamino-6-(2,4-dichlorophenoxy)-pyrimidine (22.8.3). Oxidation of this product with 3-chloroperbenzoic acid gives 2,4-diamino-6-(2,4- dichlorophenoxy)pyrimidine-3-oxide (22.8.4), the 2,4-dichlorophenoxyl group of which is replaced with a piperidine group at high temperature, giving minoxidil (22.8.5).

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Yield:38304-91-5 86.2%

Reaction Conditions:

at 103; for 4 h;Large scale;Concentration;

Steps:

1.B; 1.C; 2.B; 2.C B. Synthesis of Crude Minoxidil

13.08mol of 2,4-diamino-6-chloropyrimidine-1-oxide and 18.06kg of piperidine were added to the double-layer glass reaction kettle, the temperature was raised to 103°C with stirring, and the reaction was refluxed for 4 hours. The reaction end was monitored by TLC chromatographic plate.After the reaction was completed, the temperature was lowered to 5°C with stirring, overnight crystallization, suction filtration, the filter cake was washed with piperidine once, and dried to obtain 2.74 kg of off-white solid minoxidil crude product, the product purity was 97.39%, and the yield was 100%. .C. Synthesis of Minoxidil2.6kg of the minoxidil crude product, 6.1kg of isopropanol and 7.8kg of purified water were added to the double-layer glass reaction kettle, and the temperature was raised to 76°C with stirring, and the reflux reaction was performed for 1 hour to make the system clear; the temperature was lowered to 5°C with stirring, Crystallization overnight, suction filtration, the filter cake was washed once with isopropanol, and dried to obtain 2.24 kg of off-white solid minoxidil, the product purity was 100%, and the yield was 86.2%.

References:

CN113979952,2022,A Location in patent:Paragraph 0040; 0043-0046; 0049; 0052-0055

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