Claims
- 1. A process of preparing a compound of formula (I): wherein R1 and R2 are alkyl groups of 1 to 4 carbon atoms and n is from 2 to 5, which comprises reacting a 1-chloro-7-(protected hydroxy)-4-nitroacridin-9(10H)-one of formula (IV-P): wherein A is a hydroxy-protecting group removable by reduction, with an ω-(dialkylamino)alkylamine of formulaNH2—(CH2)nNR1R2 in which n, R1 and R2 are as defined above, to produce a 7-(protected hydroxy)-4-nitro-1-[[ω-(dialkylamino)alkyl]amino]acridin-9(10H)-one of formula (III-P): in which A, n, R1 and R2 are as defined above,reducing the compound of formula III-P at a temperature of from 15 to 50° C. with either a hydrogen-provider comprising a reducing agent able to reduce the nitro substituent and deprotect the hydroxy group in formic acid solution, or with formate ions, in the presence of a palladium catalyst and formic acid, removing substantially all the residual palladium and heating the remaining reaction mixture to effect cyclisation to the corresponding compound of formula I.
- 2. A process according to claim 1 wherein the reduction is carried out with hydrogen gas at 15 to 30° C.
- 3. A process according to claim 1 wherein the reduction is carried out with ammonium formate at a temperature of from 30 to 50° C.
- 4. A process according to claim 1, wherein the cyclisation is carried out in the presence of a strong acid.
- 5. A process according to claim 1 wherein the cyclisation is carried out in a solvent at a temperature of from 80° C. to the reflux temperature of the solvent.
- 6. A process according to claim 1 wherein the compound of formula IV-P is one in which the protected hydroxy group is a benzyloxy group.
- 7. A process according to claim 1 wherein the compound of formula I is obtained as an acid addition salt or is converted from the free base into an acid addition salt and the acid addition salt is crystallised from an ethanol-water mixture.
- 8. A process according to claim 1 wherein the amine is one in R1 and R2 are both methyl or both ethyl.
- 9. A process according to claim 8 wherein n is 2 and R1 and R2 are both ethyl.
- 10. A compound of the formula II-For: wherein R1 and R2 are alkyl groups of 1 to 4 carbon atoms and n is from 2 to 5.
- 11. A compound according to claim 10 wherein R1 and R2 are ethyl groups and n is 2.
Priority Claims (1)
Number |
Date |
Country |
Kind |
9620751 |
Oct 1996 |
GB |
|
Parent Case Info
The present application is a continuation of PCT/GB97/02470, filed Sep. 10, 1997.
Foreign Referenced Citations (2)
Number |
Date |
Country |
0 502 668 A1 |
Sep 1992 |
EP |
92 15583 |
Sep 1992 |
WO |
Non-Patent Literature Citations (2)
Entry |
Cholody et al, “Chromophore-Modified Antineoplastic . . . ,” J. Med. Chem., vol. 35, pp. 378-382 (1992). |
Cholody et al,, “Synthesis of Substituted 1,4-Diazepino . . . ,” J. Heterocyclic Chem., vol. 29, p. 1749 (1992). |
Continuations (1)
|
Number |
Date |
Country |
Parent |
PCT/GB97/02470 |
Sep 1997 |
US |
Child |
09/286655 |
|
US |