Claims
- 1. The process of making compounds of Formula IIa or IIb wherein: R1 is selected from the group consisting of hydrogen, alkyl, O-alkyl, O-cycloalkyl, cycloalkyl, cycloalkenyl, and 5 or 6 membered heterocycle substituted with one or more substituents selected from the group consisting of C1-3 alkyl, halo, OH, O-alkyl, cyano, CF3, OCF3, and substituted phenyl wherein the substituents are selected from one or more of the group consisting of hydrogen, halo, alkoxy, alkylthio, cyano, CF3, OCF3, alkyl, SO2CH3, SO2NH2, SO2NHCOalkyl, SO2NHCOalkyl, alkenyl, and alkynyl; R2 is selected from the group consisting of pyridyl, pyrimidyl, triazinyl, hydrogen, halo, alkyl, and mono- or di-substituted 6membered heterocycle wherein the substituent is selected from the group consisting of hydrogen, halo, O-alkyl, S-alkyl, cyano, CF3, OCF3, alkyl, alkylamino, dialkylamino, and mono or di-substituted phenyl optionally substituted from the group selected from hydrogen, halo, alkoxy, alkylthio, cyano, CF3, OCF3, alkyl, alkylamino and dialkylamino; R3 is selected from the group selected from hydrogen, alkyl, and phenyl wherein all but hydrogen may be substituted by one or more of the group consisting of SO2CH3, halo, alkyl, O-alkyl, S-alkyl, cyano, CF3, OCF3, and SO2NH2; R6 is selected from the group consisting of hydrogen, alkyl, phenyl, cycloalkyl and heterocyclyl which may be optionally substituted by one or more of the group consisting of phenyl, substituted phenyl, alkoxycarbonyl, acyl, halo, OH, NH2, NHR3, N(R3)2, and cyano, cycloalkyl, heterocycloalkyl, and 3-7 membered heterocycle ring; comprising: reacting an organometallic reagent of the formula R2CH2M wherein M is selected from the group consisting of Li, Na, K, and Mg, with an activated form of a carboxylic acid to produce a ketone of Formula IIc; treating the ketone of Formula IIc with a mixture of carbon disulfide and dihalo methane [such as dibromomethane or iodochloromethane] in the presence of a base and a solvent to produce the dithietane derivative of Formula IId; reacting the dithietane derivative of Formula IId with NaOR6 to produce Formula IIe condensing Formula IIe with hydrazine or substituted hydrazine.
- 2. The process of claim 1 wherein:R1 is selected from the group consisting of hydrogen, C1-6 alkyl, OC1-6 alkyl, OC3-6 cycloalkyl, C3-7 cycloalkyl, C3-7 cycloalkenyl, and 5 or 6 membered heterocycle substituted with one or more substituents selected from the group consisting of C1-3 alkyl, halo, OH, OC1-3 alkyl, cyano, CF3, OCF3, and substituted phenyl wherein the substituents are selected from one or more of the group consisting of hydrogen, halo, C1-6 alkoxy, C1-6 alkylthio, cyano, CF3, OCF3, C1-3 alkyl, SO2CH3, SO2NH2, SO2NHCOC,4 alkyl, SO2NHCOC1-4 alkyl, C1-4 alkenyl, and C1-4 alkynyl; R2 is selected from the group consisting of pyridyl, pyrimidyl, triazinyl, hydrogen, halo, C1-6 alkyl, and mono- or di-substituted 6-membered heterocycle wherein the substituent is selected from the group consisting of hydrogen, halo, OC1-6 alkyl, SC1-6 alkyl, cyano, CF3, OCF3, C1-6 alkyl, C1-6 alkylamino, C1-6 dialkylamino, and mono or di-substituted phenyl optionally substituted from the group selected from ahydrogen, halo, C1-6 alkoxy, C1-6 alkylthio, cyano, CF3, OCF3 C1-6 alky, C1-6 alkylamino and C1-6 dialkylamino; R3 is selected from the group selected from hydrogen, C1-6 alkyl, and phenyl wherein all but hydrogen may be substituted by one or more of the group consisting of SO2CH3, halo, C1-3 alkyl, OC1-3 alkyl, SC1-3 alkyl, cyano, CF3, OCF3, and SO2NH2; R6 is selected from the group consisting of hydrogen, C1-6 alkyl which may be optionally substituted by one or more of the group consisting of phenyl, substituted phenyl, halo, OH, NH2, NHR3, N(R3)2, and cyano, C3-7 cycloalkyl C3-7 heterocycloalkyl, and 3-7 membered heterocycle ring.
- 3. The process of claims 1 or 2 wherein the dihalomethane is dibromomethane.
- 4. The process of claims 1 or 2 wherein the dihalomethane isiodochloromethane.
- 5. The process of claims 1 or 2 wherein the dithietane is added to the solution of sodium alkoxide.
- 6. The process of claims 1 or 2 to produce a compound selected from the group consisting of
Parent Case Info
This application is a division of Ser. No. 09/442,471 filed Nov. 18, 1999, now U.S. Pat. No. 6,143,892, which claims priority to U.S. Provisional Application No. 60/109,177 filed Nov. 20, 1998.
Non-Patent Literature Citations (4)
Entry |
Katagiri, N.; Synthesis of Nucleosides and Related Compounds . . . ; Chem. Pharm. Bull. 1990, 12, 3242-3248. |
Okajima, N.; Synthesis of Tiocarbonyl and Heterocyclic Compounds from 2-Methylene-1, . . . ; J. Heterocyclic Chem. 1990, 27, 567-574. |
Huang, Z. N.; Synthesis of 5-Mercaptoalkylthiopyrazolyl . . . , Synth. Commun. 1996, 26, 3115-3120. |
Huang, Z. N.; Synthesis of 5-Mercaptoalkylamino-and . . . Heterocycles 1995, 41, 1653-1658. |
Provisional Applications (1)
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Number |
Date |
Country |
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60/109177 |
Nov 1998 |
US |