Claims
- 1. A process for the preparation of Compound (C) of the formula: ##STR13## in which R.sup.2 and R.sup.3 are the same and are chloro, bromo or iodo; and pharmaceutically acceptable addition salts thereof, which process comprises:
- a) nitrating a 2,3 toluene compound of the formula: ##STR14## to form compound (F) of the formula: ##STR15## b) reacting Compound (F) by forming a mixture of compound (F) with a peroxide and chlorine or bromine and irradiating the mixture in a quartz vessel with a halogen lamp to form Compound (G) of the formula: ##STR16## wherein Y.dbd.Cl or Br; c) reacting Compound (G) with a compound of the formula:
- H.sub.2 NCH.sub.2 CO.sub.2 R.sup.4
- wherein R.sup.4 is lower alkyl or H;
- to form Compound (E) of the following formula: ##STR17## d) reacting Compound (E) under reducing conditions to form Compound (B): ##STR18## e) reacting Compound (B) with CNBr, CNCl or CNl to form Compound (D): ##STR19## wherein X is Cl, Br or I; and f) reacting Compound (D) under alkaline conditions to form Compound (C).
- 2. The process of claim 1 wherein R.sup.2 and R.sup.3 are both Cl.
- 3. The process of claim 1 wherein nitration of the compound in step (a) is performed by adding an ambient temperature mixture of concentrated nitric acid and sulfuric acid slowly with stirring to the toluene compound which is maintained in an ice-water bath and then reacting the mixture at an elevated temperature to form compound (F) which is separated from other reaction products and recovered.
- 4. The process of claim 1 wherein step (c) is performed using anhydrous tetrahydrofuran as a solvent.
Parent Case Info
This is a continuation of application Ser. No. 08/566,862 filed on Dec. 4, 1995, now abandoned.
US Referenced Citations (15)
Foreign Referenced Citations (4)
Number |
Date |
Country |
278754 |
Feb 1970 |
ATX |
0 546 697 A1 |
Jun 1992 |
EPX |
17-17893 |
Sep 1942 |
JPX |
47-19261 |
Jun 1972 |
JPX |
Non-Patent Literature Citations (4)
Entry |
CA 112:216689 Kudo, 1989 Oct. 16 Preparation of Pthalimide Derivatives. |
Organic Chemistry, Morrison & Boyd 3rd Edition 1975 344-347. |
Aldrich Catalogue 1996, p. 498. |
Morrison & Boyd "Organic Chemistry" 3rd Edition 1975 pp. 387-388. |
Continuations (1)
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Number |
Date |
Country |
Parent |
566862 |
Dec 1995 |
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