Claims
- 1. A compound having the structure wherein X is O, S, SO, SO2 or NR7 where R7 is H, alkyl, aryl, alkanoyl, aroyl, alkoxycarbonyl, R7aSO2—, R7bR7cNSO2— or R7b R7cNCO;R1 and R2 are the same or different and are independently selected from alkyl, arylalkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl or cycloheteroalkyl; R4 is H, halogen, CF3, hydroxy, alkyl, alkoxy, alkanoylamino, aroylamino, cyano, alkoxyCON(R7d)—, R7fR7gNCOalkoxy- , R7eSO2N(R7d)— or R7fR7gNSO2N(R7d)—; R7a, and R7e are the same or different and are independently selected from alkyl, arylalkyl, cycloalkyl, alkenyl, cydoalkenyl, aryl, heteroaryl or cycloheteroalkyl; R7b and R7c, and R7f and R7g, and R7d are the same or different and are independently selected from H, alkyl, arylalkyl, cycloalkyl, alkenyl, aryl, heteroaryl or cycloheteroalkyl; R9 and R10 are the same or different and are independently selected from H or alkyl, or R9 and R10 may be taken together with the carbon or carbons to which they are attached to form a 3 to 7 membered carbocyclic ring;
- 2. The compound as defined in claim 1 having the following structures:
- 3. A process for preparing an intermediate of the structure: whereinX is O, S, SO, SO2 or NR7; R1 and R2 are the same or different and are independently selected from alkyl, arylalkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl or cycloheteroalkyl; R4 is H, halogen, CF3, hydroxy, alkyl, alkoxy, carboxyl, carboxylalkyl-, aminoalkyl, amino, alkanoylamino, aroylamino, cyano, alkoxyCON(R7d)—, R7fR7gNCO—, R7fR7gNCO2—, R7eSO2N(R7d)—, R7fR7gNSO2N(R7d)—, R7eOCO2— or R7eOCO—; R7a is H, alkyl, aryl, alkanoyl, aroyl, alkoxycarbonyl, R7aSO2—, R7bR7cNSO2— or R7bR7cNCO—; R7a and R7e are the same or different and are independently selected from alkyl, arylalkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl or cycloheteroalkyl, R7b and R7c, and R7f and R7g, and R7d are the same or different and are independently selected from H, alkyl, arylalkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl or cycloheteroalkyl; or R7f and R7g may be taken together with the nitrogen to which they are attached to form a stable 3 to 8 membered heterocyclic ring which, where applicable, includes a total of 1 to 3 heteroatoms in the ring, which heteroatoms may be N, O or S; R9 and R10 are the same or different and are independently selected from H or alkyl, or where at least one of R9 and R10 is alkyl, R9 and R10 may be taken together with the carbon or carbons to which they are attached to form a 3 to 7 membered carbocyclic ring; which comprisesproviding a phosphorus compound of the structure and reacting the phosphorus compound with an aldehyde of the structure under Witting conditions in the presence of a base to form intermediate 11.
- 4. The process as defined in claim 3 wherein the reaction is carried out at −78° C.
- 5. The process as defined in claim 3 wherein the base is n-butyl lithium, LiN(TMS)2 or LDA.
- 6. The process as defined in claim 3 wherein the reaction is carried out in the presence of a solvent which is THF, Et2O, toluene or DMPU.
- 7. The process as defined in claim 3 wherein the reaction is carried out at a temperature of −78° C., the base is n-butyl lithium, LiN(TMS)2 or LDA, in the presence of a solvent which is THF, Et2O, toluene or DMPU.
- 8. The process as defined in claim 7 wherein the base is n-butyl lithium, and the solvent is THF.
- 9. The process as defined in claim 3 wherein the phosphorus compound has the structure aldehyde has the structure and the intermediate 11 has the structure
- 10. The process of claim 3, further comprising the step of treating intermediate 11 with an acid to form a lactone of the structure 1a whereinX is O, S, SO, SO2 or NR7; R1 and R2 are the same or different and are independently selected from alkyl, arylalkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl or cycloheteroalkyl; R4 is H, halogen, CF3, hydroxy, alkyl, alkoxy, carboxyl, carboxylalkyl-, aminoalkyl, amino, alkanoylamino, aroylamino, cyano, alkoxyCON(R7d)—, R7fR7gNCO—, R7fR7gNCO2—, R7eSO2N(R7d)—, R7fR7gNSO2N(R7d)—, R7eOCO2— or R7eOCO—; R7 is H, alkyl, aryl, alkanoyl, aroyl, alkoxycarbonyl, R7aSO2—, R7bR7cNSO2— or R7bR7cNCO—; R7a and R7e are the same or different and are independently selected from alkyl, arylalkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl or cycloheteroalkyl, R7b and R7c, and R7f and R7g, and R7d are the same or different and are independently selected from H, alkyl, arylalkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl or cycloheteroalkyl; or R7f and R7g may be taken together with the nitrogen to which they are attached to form a stable 3 to 8 membered heterocyclic ring which, where applicable, includes a total of 1 to 3 heteroatoms in the ring, which heteroatoms maybe N, O or S; R9 and R10 are the same or different and are independently selected from H or alkyl, or where at least one of R9 and R10 is alkyl, R9 and R10 may be taken together with the carbon or carbons to which they are attached to form a 3 to 7 membered carbocyclic ring.
- 11. The process of claim 10 wherein the lactone has the structure.
- 12. The process as defined in claim 10 wherein the acid is trifluoroacetic acid or hydrochloric acid.
Parent Case Info
This application is the divisional of U.S. application Ser. No. 10/007,407, filed on Dec. 4, 2001, now U.S. Pat. No. 6,627,636, which is a continuation-in-part of U.S. application Ser. No. 09/875,155 filed Jun. 6, 2001 abandoned which application claims priority from U.S. provisional application No. 60/211,595, filed Jun. 15, 2000.
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|
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