Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-01-03
1996-06-04
Richter, Johann
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
544122, 544370, 546146, 546168, 546210, 5462751, 5462747, 5462744, 548518, 5483641, 548200, 548215, C07D23364, C07D41312
Patent
active
055234100
DESCRIPTION:
BRIEF SUMMARY
This is a 371 of PCT/JP93/00885 filed Jun. 28, 1993.
TECHNICAL FIELD
The present invention relates to a novel synthetic intermediate for preparing amino acid derivatives possessing renin-inhibitory activity, and to processes for preparing the amino acid derivatives using said synthetic intermediate.
BACKGROUND ART
The amino acid derivative of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.10 are as defined later, is known to have renin-inhibitory activity and to be useful for the treatment of hypertensions such as essential hypertension, renal hypertension, and malignant hypertention, heart failure, and the like. EP-A-300189 discloses the following synthetic method For preparing said compound. ##STR2## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.10 are as defined later.
The aforementioned method is, however, not entirely satisfactory as an industrial preparation method in that a starting material (VI) is relatively expensive and the total yield of the processes as a whole is as low as about 40-50%, thus rendering preparation cost of the object final product amino acid derivatives (I) considerably high.
DISCLOSURE OF THE INVENTION
Accordingly, an object of the present invention is to solve such problems of the conventional method by providing industrially advantageous processes for preparing the amino acid derivatives (I) at high yields from a less expensive starting material.
Another object of the present invention is to provide an intermediate for the preparation of the amino acid derivatives (I), which is synthesized from a less expensive starting material.
The present inventors have found that the amino acid derivatives (I) can be obtained at high yields from a less expensive starting material via a compound (II) which is a novel intermediate to be mentioned later, and completed the present invention.
Accordingly, the present invention relates to a compound (II) of the formula ##STR3## wherein R.sup.1 is lower alkyl which may be substituted by a substituent selected from the group consisting of acyl, hydroxyl, lower alkoxy, aryl, lower alkylthio and a group of the formula ##STR4## (wherein R.sup.6 is hydrogen or acyl, and R.sup.7 is hydrogen or lower alkyl); aryl; or amino which may be substituted by substituent(s) selected from the group consisting of lower alkyl and acyl; the attached nitrogen atom form a heterocyclic group which may be substituted by substituent (s) selected from the group consisting of lower alkyl, hydroxy(lower)alkyl, lower alkoxy(lower)alkyl, acyl(lower)alkyl, oxo and acyl;
According to the present invention, the compound (I) of the formula ##STR5## wherein R.sup.10 is lower alkyl, and R.sup.1, R.sup.2, and R.sup.3 are as defined above, and a salt thereof can be prepared by reacting a compound (IIa) of the formula ##STR6## wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are as defined above, or its reactive derivative at the carboxyl group or a salt thereof with a compound (III) of the formula ##STR7## wherein R.sup.10 is as defined above, or its reactive derivative at the amino group or a salt thereof, followed by elimination of the N-protective group, if necessary (hereinafter this process is to be referred to as Process a).
According to the present invention, the compound (I) and a salt thereof can be prepared by reacting a compound (IV) of the formula ##STR8## wherein R.sup.1 and R.sup.2 are as defined above, or its reactive derivative at the carboxyl group or a salt thereof with a compound (V) of the formula ##STR9## wherein R.sup.3, R.sup.4, and R.sup.5 are as defined above, or its reactive derivative at the amino group or a salt thereof to give a compound (II) of the formula ##STR10## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are as defined above, or a salt thereof, and reacting the obtained compound (II) or its reactive derivative at the carboxyl group or a salt thereof with a compound (III) of the formula ##STR11## wherein R.sup.10 is as defined above, or its reactive derivative at the amino group or a salt thereof, follo
REFERENCES:
patent: 5142048 (1992-08-01), Hemmi et al.
Morrison, R. T. et al., Organic Chemistry, 5th ed., Allyn and Bacon, Inc., Boston, 1987.
Furutera Tetsuo
Kagara Kooji
Kawai Nobutaka
Machiya Koji
Nakamura Takashi
Cross Laura R.
Fujisawa Pharmaceutical Co. Ltd.
Richter Johann
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