Unlock instant, AI-driven research and patent intelligence for your innovation.

Method for preparing aliskiren intermediate

A technology for intermediates and compounds, which is applied in the field of preparation of aliskiren intermediate compounds, can solve the problems of long reaction time, increased cost, environmental impact, etc., and achieves the effects of long reaction time, reduced impact and easy operation.

Active Publication Date: 2013-06-12
NINGBO MENOVO PHARMA
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] All of the above documents disclose that 4-methoxy-3-hydroxy-benzaldehyde is used as raw material to prepare 4-methoxy-3-(3-methoxypropoxy)-benzyl alcohol through 2-3 steps of reaction , the reaction time is long, the operation is complicated, and the intermediates need to be separated to increase the cost and have a certain impact on the environment.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for preparing aliskiren intermediate
  • Method for preparing aliskiren intermediate
  • Method for preparing aliskiren intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Add 4-methoxy-3-hydroxy-benzaldehyde (50g, 0.33mol), 3-methoxy-1-bromopropane (75g, 0.49mol), potassium carbonate (67g, 0.485mol) into a 500mL three-necked flask ) and 250mL ethanol, heated to reflux for 4 hours, then cooled to 20°C, added sodium borohydride (6.0g, 0.16mol), reacted for 10 minutes, concentrated under reduced pressure and distilled ethanol, then added 250mL water, 150mL dichloromethane, Stand to separate layers, extract the water phase with 50ml of dichloromethane for 2 times, combine the dichloromethane layers, wash 3 times with 150ml of water each time, dry and filter with anhydrous sodium sulfate, concentrate to obtain the aliskiren intermediate compound 4- Methoxy-3-(3-methoxypropoxy)-benzyl alcohol 71.68 g. (Molar yield: 96%)

[0038] H-NMR (CDCl 3 ): 6.80-6.95 (m, 3H), 4.58 (d, 2H), 4.11 (t, 2H), 3.84 (s, 3H), 3.56 (t, 2H), 2.33 (s, 3H), 2.11 (m, 2H), 1.95(t, 1H).

Embodiment 2

[0040] Add 4-methoxy-3-hydroxy-benzaldehyde (50g, 0.33mol), 3-methoxy-1-bromopropane (60g, 0.39mol), potassium carbonate (45g, 0.33mol) into a 500mL three-necked flask ) and 250mL ethanol, heated to reflux for 9 hours, then cooled to 5°C, added sodium borohydride (4.5g, 0.12mol), reacted for 45 minutes, concentrated under reduced pressure and evaporated ethanol, then added 250mL water, 150mL dichloromethane, Stand and separate layers, extract the water phase with 50 mL of dichloromethane for 2 times, combine the dichloromethane layers, wash 3 times with 100 mL of water each time, dry and filter with anhydrous sodium sulfate, concentrate to obtain the aliskiren intermediate compound 4- Methoxy-3-(3-methoxypropoxy)-benzyl alcohol 69.8 g. (Molar yield: 93.5%)

[0041] H-NMR (CDCl 3 ): 6.80-6.96 (m, 3H), 4.59 (d, 2H), 4.15 (t, 2H), 3.84 (s, 3H), 3.60 (t, 2H), 2.35 (s, 3H), 2.12 (m, 2H), 1.93(t, 1H).

Embodiment 3

[0043] Add 4-methoxy-3-hydroxy-benzaldehyde (40g, 0.26mol), 3-methoxy-1-bromopropane (43.8g, 0.286mol), potassium carbonate (44g, 0.32 mol) and 200mL ethanol, heated to reflux for 7 hours, then cooled to 10°C, added sodium borohydride (2.9g, 0.078mol), reacted for 30 minutes, concentrated under reduced pressure and evaporated ethanol, then added 200mL water, 120mL dichloromethane , standing and layering, the aqueous phase was extracted twice with 50 mL of dichloromethane, the combined dichloromethane layers were washed with 100 mL of water three times each time, dried and filtered over anhydrous sodium sulfate, and then concentrated to obtain the aliskiren intermediate compound 4 - Methoxy-3-(3-methoxypropoxy)-benzyl alcohol 55.9 g. (Molar yield: 95%)

[0044] H-NMR (CDCl 3 ): 6.80-6.90 (m, 3H), 4.55 (d, 2H), 4.15 (t, 2H), 3.85 (s, 3H), 3.60 (t, 2H), 3.35 (s, 3H), 2.10 (m, 2H), 1.90(t, 1H).

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a method for preparing an aliskiren intermediate, which comprises the following steps of: stirring and mixing 4-methoxy-3-hydroxy-benzaldehyde, 3-methoxy-1-bromopropane and potassium carbonate in an ethanol solvent, heating and refluxing, and reacting for 2 to 9 hours; reducing the temperature to be between 5 and 20 DEG C, adding sodium borohydride and performing reduction reaction for 10 to 50 minutes; concentrating under reduced pressure to evaporate ethanol, adding water and dichloromethane, standing for demixing, extracting a water phase by using the dichloromethane, mixing dichloromethane layers, and washing by using the water; and drying by using anhydrous sodium sulfate, and concentrating to obtain an aliskiren intermediate compound 4-methoxy-3-(3-methoxypropoxy)-benzyl alcohol. The reaction can be performed in the same reaction container, so that reaction time is shortened, the method is easy and convenient to operate, and the intermediate is not required to be separated; therefore, cost is reduced, and the influence on an environment is reduced simultaneously.

Description

technical field [0001] The invention relates to a method for preparing a drug intermediate for treating hypertension, in particular to a method for preparing an aliskiren intermediate compound, and belongs to the technical field of drug preparation methods. Background technique [0002] Aliskiren (Aliskiren) is the first antihypertensive drug approved by the US FDA to directly inhibit the renal enzyme renin that causes blood pressure to increase. Combining it with the diuretic hydrochlorothazine can further lower blood pressure, and the antihypertensive effect is better than that of each alone medication. [0003] The chemical name of Aliskiren is: (2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2-methylpropyl)-4-hydroxy-2-isopropyl-7 -[4-Methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide, the structural formula is shown in Formula I: [0004] The important intermediate of Aliskiren is: 4-methoxy-3-(3-methoxypropoxy)-benzyl alcohol, whose chemical structure is shown in IV: [...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07C43/23C07C41/26
Inventor 焦华沈谨志陈昱王涛
Owner NINGBO MENOVO PHARMA