Claims
- 1. A compound of the formula or a pharmaceutically acceptable salt thereof,wherein R1 and R2 are each independently hydrogen or methyl; andR3, R4, R5 and R6 are each independently H, halo, formyl, (C1-C6)alkyl optionally substituted with up to three fluoro, (C1-C6)alkoxy optionally substituted with up to three fluoro, (C1-C6)alkoxycarbonyl, (C1-C6)alkylenyloxycarbonyl, (C1-C4)alkoxy-(C1-C4)alkyl, (C1-C4)alkylcarbonylamido, (C3-C7)cycloalkylcarbonylamido, phenylcarbonylamido, benzyl, phenyl or naphthyl, wherein said benzyl, phenyl and naphthyl are optionally independently with up to two substituents independently selected from halo, (C1-C6)alkyl optionally substituted with up to three fluoro, (C1-C6)alkoxy optionally substituted with up to three fluoro and (C1-C4)alkoxy-(C1-C4)alkyl.
- 2. A compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3, R4, R5 and R6 are each independently hydrogen, methyl, methoxy, chloro, fluoro, ethyl, 4-fluorophenyl, trifluoromethyl, isopropyl or phenyl.
- 3. A compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R1, R2, R4 and R5 are each hydrogen; R3 is 3-methyl and R6 is 5-chloro, having the structure
- 4. A process for preparing a compound of the formula wherein R1 and R2 are each independently hydrogen or methyl;R3, R4, R5 and R6 are each independently H, halo, formyl, (C1-C6)alkyl optionally substituted with up to three fluoro, (C1-C6)alkoxy optionally substituted with up to three fluoro, (C1-C6)alkoxycarbonyl, (C1-C6)alkylenyloxycarbonyl, (C1-C4)alkoxy-(C1-C4)alkyl, (C1-C4)alkylcarbonylamido, (C3-C7)cycloalkylcarbonylamido, phenylcarbonylamido, benzyl, phenyl or naphthyl, wherein said benzyl, phenyl and naphthyl are optionally independently with up to two substituents independently selected from halo, (C1-C6)alkyl optionally substituted with up to three fluoro, (C1-C6)alkoxy optionally substituted with up to three fluoro and (C1-C4)alkoxy-(C1-C4)alkyl;comprising the consecutive steps of:(a) reacting a compound of the formula wherein R3, R4, R5 and R6 are each independently defined as set forth above, with an organolithium compound in the presence of a sulfur source in a reaction inert solvent to form a reactive intermediate of the formula (b) reacting said reactive intermediate IIa with a compound of the formula to form a compound of the formula IV.
- 5. A process of claim 4 wherein said organolithium compound is n-butyllithium, said reaction inert solvent is tetrahydrofuran and said sulfur source is S8.
- 6. A process of claim 4 or 5 wherein R3, R4, R5 and R8 are each independently hydrogen, methyl, methoxy, chloro, fluoro, ethyl, 4-fluorophenyl, trifluoromethyl, isopropyl or phenyl.
- 7. A process of claim 6 wherein R1, R2, R4 and R5 are each hydrogen; R3 is 3-methyl and R6 is 5-chloro.
- 8. A process for preparing the compound of the formula comprising the consecutive steps of:(a) reacting the compound of the formula with n-butyllithium in the presence of S8 in tetrahydrofuran to form the reactive intermediate (b) reacting said reactive intermediate XIIa with the compound of the formula to form the compound of the formula (c) reacting said compound of the formula XIV with sodium methoxide in methanol to form the compound of the formula (d) reacting said compound of the formula XV with concentrated hydrochloric acid to form the compound of the formula (e) oxidizing said compound of the formula XVI with hydrogen peroxide urea complex in the presence of trifluoroacetic anhydride in tetrahydrofuran to form a compound of the formula XI.
- 9. The process of claim 8 wherein step (c) and step (d) are performed in situ.
- 10. A process for preparing a compound of the formula wherein R1 and R2 are each independently hydrogen or methyl; and R3, R4, R5 and R6 are each independently h, halo, formyl, (C1-C6)alkyl optionally substituted with up to three fluoro, (C1-C6)alkoxy optionally substituted with up to three fluoro, (C1-C6)alkoxycarbonyl, (C1-C6)alkylenyloxycarbonyl, (C1-C4)alkoxy-(C1-C4)alkyl, (C1-C4)alkylcarbonylamido, (C3-C7)cycloalkylcarbonylamido, phenylcarbonylamido, benzyl, phenyl or naphthyl, wherein said benzyl, phenyl and naphthyl are optionally independently with up to two substituents independently selected from halo, (C1-C6)alkyl optionally substituted with up to three fluoro, (C1-C6)alkoxy optionally substituted with up to three fluoro and (C1-C4)alkoxy-(C1-C4)alkyl;comprising the consecutive steps of:(a) reacting a compound of the formula wherein R3, R4, R5 and R6 are each independently defined as set forth above, with an organolithium compound in the presence of a sulfur source in a first reaction inert solvent to form the reactive intermediate (b) reacting said reactive intermediate IIa with a compound of the formula to form a compound of the formula (c) reacting said compound of the formula IV with an alkaline (C1-C2)alkoxide in a (C1-C2)alkanol to form an ether compound of the formula wherein Alk is (C1-C2)alkyl;(d) reacting said compound of the formula V with a mineral acid to form a compound of the formula (e) oxidizing said compound of the formula VI in a second reaction inert solvent to form a compound of the formula I.
- 11. The process of claim 10 wherein step (c) and step (d) are performed in situ.
- 12. The process of claim 11 wherein in step (a) said organolithium compound is n-butyllithium, said first reaction inert solvent is tetrahydrofuran and said sulfur source is S8; in step (c) said alkaline (C1-C2)alkoxide is sodium methoxide and said (C1-C2)alkanol is methanol; and in step (d) said compound of formula VI is oxidized with urea-hydrogen peroxide in the presence of trifluoroacetic anhydride and said second reaction inert solvent is tetrahydrofuran.
- 13. A process of any one of claims 10-12 wherein R3, R4, R5 and R6 are each independently hydrogen, methyl, methoxy, chloro, fluoro, ethyl, 4-fluorophenyl, trifluoromethyl, isopropyl or phenyl.
- 14. A process of claim 13 wherein R1, R2, R4 and R5 are each hydrogen; R3 is 3-methyl and R6 is 5-chloro.
Parent Case Info
This application is filed claiming priority from U.S. Application No. 60/347,679 filed Jan. 9, 2002.
Foreign Referenced Citations (2)
Number |
Date |
Country |
135076 |
Jul 1984 |
EP |
WO 02079198 |
Oct 2002 |
WO |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/347679 |
Jan 2002 |
US |