Claims
- 1. A process for the preparation of a compound of formula: ##STR85## or a pharmaceutically acceptable acid addition salt thereof wherein: R.sup.1 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, arylloweralkyl, cyclopropylloweralkyl;
- R.sup.2 and R.sup.3 are each independently hydrogen, lower alkyl, hydroxy, lower alkoxy, halogen, amino, monoloweralkyamino or diloweralkylamino;
- m is an integer of from 0 to 2 ; and
- n is an integer of from 2 to 4; consisting essentially of:
- (a) reacting a compound of formula III ##STR86## with lithioacetonitrile in a solvent at a temperature of from about -78.degree. C. to about 20.degree. C. to produce a compound of formula IV: ##STR87## (b) hydrogenating catalytically a compound from step (a) a solvent under a hydrogen atmosphere to produce a compound of formula V wherein n is 2; ##STR88## (c) reacting a compound from step (b) with an alkylchloroformate in the presence of trialkylamine in a solvent to produce a compound of formula IX, wherein R.sup.5 is an acid stable protecting group selected from methyl, ethyl, 2,2,2-trichloroethyl, (-)-methanol, or (-)-.alpha.-methylbenzyl; ##STR89## (d) reacting a compound from step (c) with an acid to produce a compound of formula X; and ##STR90## (e) reacting a compound from step (d) to remove the carbamate functionality with zinc dust in alcohol in the presence of a weak acid to produce the desired compound of formula I and ##STR91## isolating or converting to a pharmaceutically acceptable salt thereof.
- 2. A process according to claim 1 wherein in step (e) a compound from step (d) is reduced in the presence of lithium aluminum hydride or diborane in a solvent selected from ether and tetrahydrofuran to produce a compound of formula I wherein R is methyl, and isolating or converting to a pharmaceutically acceptable salt thereof.
- 3. A process for the preparation of a compound of formula V consisting essentially of: ##STR92## (a) reacting a compound of formula III ##STR93## with a compound of formula VI ##STR94## to produce a compound of formula VII ##STR95## (b) reacting a compound produced in step (a) with ammonia in a solvent to produce a compound of formula VIII ##STR96## (c) reacting a compound from step (b) with a reducing agent in a solvent to produce the compound of formula V wherein n is 3.
Parent Case Info
This is a divisional application of U.S. Ser. No. 07/677,029 filed Mar. 28, 1991, now U.S. Pat. No. 5,070,093, which is a divisional application of U.S. Ser. No. 07/565,306 filed Aug. 9, 1990, now U.S. Pat. No. 5,109,136.
US Referenced Citations (9)
Non-Patent Literature Citations (2)
Entry |
T. A. Lyle et al., "Structure and Activity of Hydrogenated Derivatives of (+)-5-Methyl-10, 11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK-801)", J. Med. Chem. 1990, 33, 1047-1052. |
W. J. Thompson et al., "Synthesis and Pharmacological Evaluation of a Series of Dibenzo[a,d]cycloalkenimines as N-Methyl-D-aspartate Antagonists", J. Med. Chem., 1990, 33, 789-808. |
Divisions (2)
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Number |
Date |
Country |
Parent |
677029 |
Mar 1991 |
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Parent |
565306 |
Aug 1990 |
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