TW343972B - Process for the preparation of an endothelin antagonist - Google Patents
Process for the preparation of an endothelin antagonistInfo
- Publication number
- TW343972B TW343972B TW085114918A TW85114918A TW343972B TW 343972 B TW343972 B TW 343972B TW 085114918 A TW085114918 A TW 085114918A TW 85114918 A TW85114918 A TW 85114918A TW 343972 B TW343972 B TW 343972B
- Authority
- TW
- Taiwan
- Prior art keywords
- formula
- give
- acid
- solvent
- reacting
- Prior art date
Links
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
Abstract
A process for the preparation of a compound of the structural formula I: (I) in which the * represents a chiral center; comprising the steps of: a) reacting the methyl 4-hydroxy-3-n-propylbenzoate with a base in an aprotic inert solvent to give a salt of methyl 4-hydroxy-3-n-propylbenzoate (formula) in which: M+ is Na+, K+, or Li+ ; b) acylating 1,3-benzodioxole with ethyl oxalyl chloride in the presence of a lewis acid and an organic solvent to give an ester (formula) c) hydrolyzing the ester with a base in a solvent to give an acid (formula) d) reacting the acid with a chlorinating agent in a solvent to give an acid chloride (formula) e) reacting the acid chloride with a chiral auxiliary, Rc, and an organic base to give a substituted ketoester derivative (formula) in which: Rc is (formulae) Ra is (C1 -C6)-alkyl, phenyl, or cyclohexyl; R13 is (C1 -C6)-alkyl, phenyl or cyclohexyl; R14 and R15 are independently: (C1 -C10)-alkyl, or R14 and R15 can join together to form a 5- or 6-membered heterocyclic ring selected from the group consisting of: piperadinyl or pyrrolidinyl; f) reducing the substituted ketoester derivative with a reducing agent to give a hydroxyl derivative (formula) g) halogenating the hydroxyl derivative with a halogenating agent in an organic solvent to give a halo derivative (formula) in which: X is Br, Cl, or I; h) alkylating the salt of methyl 4-hydroxy-3-n-propylbenzoate with the halo derivative, in an organic solvent to give a chiral auxiliary phenoxyphenylacetic acid derivative (formula) I) hydrolyzing the chiral auxiliary from the phenoxyphenylacetic acid derivative to give a phenoxyphenylacetic acid (formula) j) reacting the phenoxyphenylacetic acid with a chlorinating agent in a solvent to give an acid chloride (formula) k) reacting the acid chloride with a source of ammonia to give an amide (formula) l) alkylating the amide with 4-isopropylbenzenesulfonyl chloride in the presence of a base and a solvent to give a sulfonamide (formula) m) hydrolyzing the sulfonamide with an inorganic base in a solvent to give a salt of the acid (formula) n) neutralizing the salt with mineral acid to give a diacid (formula) o) reacting the diacid with two equivalents of α-methylbenzylamine in an organic solvent to give a diastereomeric salt (formula) p) breaking the salt with mineral acid to give an optically enriched acid (formula) q) reacting the optically enriched acid with a base in a solvent or mixture of solvents to give a dipotassium salt, the compound of formula I (formula).
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US875695P | 1995-12-12 | 1995-12-12 | |
GBGB9603243.8A GB9603243D0 (en) | 1996-02-16 | 1996-02-16 | Process for the preparation of an endothelin antagonist |
Publications (1)
Publication Number | Publication Date |
---|---|
TW343972B true TW343972B (en) | 1998-11-01 |
Family
ID=10788847
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW085114918A TW343972B (en) | 1995-12-12 | 1996-12-03 | Process for the preparation of an endothelin antagonist |
Country Status (3)
Country | Link |
---|---|
AR (1) | AR005042A1 (en) |
GB (1) | GB9603243D0 (en) |
TW (1) | TW343972B (en) |
-
1996
- 1996-02-16 GB GBGB9603243.8A patent/GB9603243D0/en active Pending
- 1996-11-12 AR ARP960105619A patent/AR005042A1/en unknown
- 1996-12-03 TW TW085114918A patent/TW343972B/en active
Also Published As
Publication number | Publication date |
---|---|
AR005042A1 (en) | 1999-04-07 |
GB9603243D0 (en) | 1996-04-17 |
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