Method for purifying urapidil with counter solvent recrystallization method

Abstract

The invention discloses a method for purifying urapidil, in particular to a method for purifying urapidil with a counter solvent recrystallization method, belonging to the field of purification of compounds. The method is implemented by the following steps of: adding urapidil of which the purity is over 96 percent into an organic solvent; heating and dissolving; performing suction filtration; pouring the filtrate into a counter solvent; standing; performing suction filtration under reduced pressure; and performing vacuum drying to obtain the urapidil. The method has the advantages of simpleness in operation, short time needed for precipitating a product, higher yield of the obtained urapidil than that of the prior art, and purity of over 99.82 percent (HPLC (High Performance Liquid Chromatography)); and the method is extremely suitable for industrial production.

Description

technical field

[0001] The invention relates to a method for purifying uradil, in particular to a method for purifying uradil by using an anti-solvent recrystallization method, and belongs to the field of compound purification. Background technique

[0002] Urapidil (Urapidil) is uracil substituted by benzoxinazole, its chemical name is 6-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]-propyl]-amino] -1, 3-Dimethyl-2, 4(1H, 3H)-pyrimidinedione, the English name is 6-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]amino]-1 ,3-dimethyl-2, 4(1H, 3H)-pyrimidinedione, the structural formula is:

[0003]

[0004] The trade names of urapidil hydrochloride are Ningding, Ebrantil and Lixidine. Its mechanism of action is 1 Receptor blockers and weaker β-receptor blockers have both peripheral and central hypotensive effects. Peripheral Major Blockade Alpha 1 receptor, and excitatory central 5-HT 1A Receptors, thereby reducing the sympathetic feedback regulation of the medullary cardiova...

Examples

Embodiment 1

[0019] Add 5g of urapidil (purity 96.16%) into 15ml of dichloromethane, heat it at 40°C to dissolve it, and suction filter it while it is hot. White turbidity appeared, let it stand for 0.5h, vacuum-filtered under reduced pressure, and the obtained solid was vacuum-dried at room temperature to obtain 4.87g of urapidil, with a yield of 97.4% and a purity of 99.98%.

[0020] Product purity was detected by Shimadzu LC-10ATvp high performance liquid chromatography (SPD-10ATvp detector),

[0021] Detection method: National New Drug Standard [WS1-(X-116)-2003Z].

[0022] attached figure 1 The HPLC analysis result of urapidil standard substance is as follows:

[0023] attached figure 2 The HPLC analysis result of urapidil before experimental example 1 anti-solvent recrystallization is as follows:

[0024] attached image 3 The HPLC analysis result of urapidil after experimental example 1 anti-solvent recrystallization is as follows:

[0025]

Embodiment 2

[0027] Add 5 g of urapidil (purity 96.16%) into 15 ml of DMSO, heat it at 45°C to dissolve it, and suction filter it while it is hot. Set aside for 0.5h, filter under reduced pressure, and dry the obtained solid under vacuum at room temperature to obtain 4.79g of urapidil, with a yield of 95.8% and a purity of 99.98%.

Embodiment 3

[0029] Add 5g of urapidil (purity 96.16%) into 15ml of THF, heat it at 45°C to dissolve it, and suction filter it while it is hot. White turbidity appeared rapidly, left standing for 0.5h, vacuum filtration under reduced pressure, and the resulting solid was vacuum-dried at room temperature to obtain 4.67g of urapidil with a yield of 93.4% and a purity of 99.93%.

technical field

[0001] The invention relates to a method for purifying uradil, in particular to a method for purifying uradil by using an anti-solvent recrystallization method, and belongs to the field of compound purification. Background technique

[0002] Urapidil (Urapidil) is uracil substituted by benzoxinazole, its chemical name is 6-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]-propyl]-amino] -1, 3-Dimethyl-2, 4(1H, 3H)-pyrimidinedione, the English name is 6-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]amino]-1 ,3-dimethyl-2, 4(1H, 3H)-pyrimidinedione, the structural formula is:

[0003]

[0004] The trade names of urapidil hydrochloride are Ningding, Ebrantil and Lixidine. Its mechanism of action is 1 Receptor blockers and weaker β-receptor blockers have both peripheral and central hypotensive effects. Peripheral Major Blockade Alpha 1 receptor, and excitatory central 5-HT 1A Receptors, thereby reducing the sympathetic feedback regulation of the medullary cardiova...

Examples

Embodiment 1

[0019] Add 5g of urapidil (purity 96.16%) into 15ml of dichloromethane, heat it at 40°C to dissolve it, and suction filter it while it is hot. White turbidity appeared, let it stand for 0.5h, vacuum-filtered under reduced pressure, and the obtained solid was vacuum-dried at room temperature to obtain 4.87g of urapidil, with a yield of 97.4% and a purity of 99.98%.

[0020] Product purity was detected by Shimadzu LC-10ATvp high performance liquid chromatography (SPD-10ATvp detector),

[0021] Detection method: National New Drug Standard [WS1-(X-116)-2003Z].

[0022] attached figure 1 The HPLC analysis result of urapidil standard substance is as follows:

[0023] attached figure 2 The HPLC analysis result of urapidil before experimental example 1 anti-solvent recrystallization is as follows:

[0024] attached image 3 The HPLC analysis result of urapidil after experimental example 1 anti-solvent recrystallization is as follows:

[0025]

Embodiment 2

[0027] Add 5 g of urapidil (purity 96.16%) into 15 ml of DMSO, heat it at 45°C to dissolve it, and suction filter it while it is hot. Set aside for 0.5h, filter under reduced pressure, and dry the obtained solid under vacuum at room temperature to obtain 4.79g of urapidil, with a yield of 95.8% and a purity of 99.98%.

Embodiment 3

[0029] Add 5g of urapidil (purity 96.16%) into 15ml of THF, heat it at 45°C to dissolve it, and suction filter it while it is hot. White turbidity appeared rapidly, left standing for 0.5h, vacuum filtration under reduced pressure, and the resulting solid was vacuum-dried at room temperature to obtain 4.67g of urapidil with a yield of 93.4% and a purity of 99.93%.

Images