Sacubitril intermediate and preparation method thereof
AssigneeSunshine Lake Pharma Co., Ltd.
InventorsLei CHEN, Guodong SUN, Xiaodong HAN, Shun LI, Jiebin ZENG, Zhongqing WANG, Zhonghua LUO
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Abstract
The present invention relates to a sacubitril intermediate and a preparation method thereof. The sacubitril intermediate disclosed herein can be prepared by a deprotection reaction of a compound. In addition, the intermediate can be used as a raw material to synthesize sacubitril. The method disclosed herein has advantages of easily obtained raw materials, simple preparation process, low cost, environment friendly, and etc., which is very suitable for industrial production.
Claims22
A compound of Formula (V),
- wherein:
- R1 is phenyl, methoxy, hydroxy, chloro, bromo, iodo, mesylate, triflate or 4-methylbenzenesulfonate;
- R2 is
- and when R1 is phenyl, R2 is not
- R3 is H, —(C1-C4)alkyl or —(C1-C4)alkyl-aryl;
- and
- R4 is H, —(C1-C4)alkyl, —(C3-C6)heterocyclyl, —(C1-C4)alkyl-aryl, trimethylsilyl, triethylsilyl or t-butyldimethylsilyl.
A method of preparing a compound of Formula (V):
- wherein the compound of Formula (V) is prepared by a deprotection reaction of a compound of Formula (IV):
- in the presence of a base or an acid, wherein:
- R1 is phenyl, methoxy, hydroxy, chloro, bromo, iodo, mesylate, triflate or 4-methylbenzenesulfonate;
- R2 is
- and when R1 is phenyl, R2 is not
- R3 is H, —(C1-C4)alkyl or —(C1-C4)alkyl-aryl;
- R4 is H, —(C1-C4)alkyl, —(C3-C6)heterocyclyl, —(C1-C4)alkyl-aryl, trimethylsilyl, triethylsilyl or t-butyldimethylsilyl;
- and
- R5 is H, —(C1-C4)alkyl or —(C1-C4)alkyl-aryl.
A method of preparing sacubitril,
- comprising the following steps:
- a) preparing a compound of Formula (VI) by an enzymic catalytic reaction of a compound of Formula (V) in the presence of ω-transaminase and phosphopyridoxal,
- b) optionally, preparing a compound of Formula (VII) from the compound of Formula (VI):
- and
- c) preparing sacubitril from the compound of Formula (VII),
- wherein:
- R1 is phenyl, methoxy, hydroxy, chloro, bromo, iodo, mesylate, triflate or 4-methylbenzenesulfonate;
- R2 is
- R3 is H, —(C1-C4)alkyl or —(C1-C4)alkyl-aryl;
- and
- R4 is H, —(C1-C4)alkyl, —(C3-C6)heterocyclyl, —(C1-C4)alkyl-aryl, trimethylsilyl, triethylsilyl or t-butyldimethylsilyl.
Dependencies are inferred from the claim text.