Claims
- 1. A one pot process for preparing a compound of the formula formula (1) ##STR29## wherein Ar is substituted phenyl or pyridyl;
- R.sup.1 is methyl;
- HET is a group selected from ##STR30## R.sup.2 is selected from H, halo, lower alkyl, (C.sub.7 -C.sub.21) straight chain alkyl, hydroxy, lower alkoxy, haloalkyl, haloalkoxy, alkoxyalkyl, alkoxyalkoxy, lower alkenyl, haloalkenyl, CN, NO.sub.2, CO.sub.2 R.sup.6, CON(R.sup.6).sub.2, (C.sub.3 -C.sub.6) cycloalkyl, S(O).sub.m R.sup.6, SCN, pyridyl, substituted pyridyl, isoxazolyl, substituted isoxazolyl, naphthyl, substituted naphthyl, phenyl, substituted phenyl, --(CH.sub.2).sub.n R.sup.6, --CH.dbd.CHR.sup.6, --C.tbd.-CR.sup.6, --CH.sub.2 OR.sup.6, --CH.sub.2 SR.sup.6, --CH.sub.2 NR.sup.6 R.sup.6, --OCH.sub.2 R.sup.6, --SCH.sub.2 R.sup.6, --NR.sup.6 CH.sub.2 R.sup.6, ##STR31## R.sup.3 and R.sup.4 are independently H, halo, lower alkyl, lower alkoxy, haloalkyl, haloalkoxy, CN, CO.sub.2 R.sup.6, CON(R.sup.6).sub.2, or S(O).sub.m alkyl, or
- if R.sup.3 and R.sup.4 are attached to adjacent carbon atoms, they may join to form a 5 or 6 member saturated or unsaturated carbocyclic ring which may be substituted by 1 or 2 halo, lower alkyl, lower alkoxy or haloalkyl groups;
- if R.sup.2 and R.sup.3 are attached to adjacent carbon atoms, they may combine to form a 5 or 6 member saturated or unsaturated carbocyclic ring which may be substituted by 1 or 2 halo, lower alkyl, lower alkoxy or haloalkyl groups;
- R.sup.5 is H, lower alkyl, haloalkyl, lower alkenyl, lower alkynyl, phenyl, or substituted phenyl;
- R.sup.6 is H, lower alkyl, haloalkyl, lower alkenyl, lower alkynyl, phenyl, or substituted phenyl;
- m is 0, 1, or 2; and
- n is 1 or 2;
- p is an integer from 2 to 6;
- which comprises the steps of:
- (a) reacting a compound of formula (2) ##STR32## wherein Ar is as defined in formula (1) and R.sup.7 is lower alkyl, or an acid addition salt thereof, with an acid chloride of the formula (3) ##STR33## wherein HET is as defined in formula (1), in 1,2-dichloroethane in the presence of an organic or inorganic .sub.-- base to produce the adduct-intermediate of formula (4) ##STR34## wherein Ar, R.sup.7, and HET are as defined above, and (b) without isolating said adduct-intermediate, adding methyl hydrazine to the reaction mixture to produce the compound of formula (1), and
- (c) adding octane to the reaction mixture to crystallize the product of formula (1).
- 2. A process of claim 1 wherein an acid addition salt of the compound of formula (2) is used.
- 3. A process of claim 2 wherein the hydrogen iodide or methyl sulfate salt of the compound of formula (2) is used.
- 4. A process of claim 1 wherein a compound of formula (2) ##STR35## wherein Ar is substituted phenyl and R.sup.7 is lower alkyl, or an acid addition salt thereof, is reacted with an acid chloride of the formula (3a) ##STR36## wherein Y, R.sup.2, R.sup.3, and R.sup.4 are as defined in formula (1), to produce an adduct-intermediate of formula (4a) ##STR37## wherein Ar, Y, R.sup.2, R.sup.3, R.sup.4 and R.sup.7 are as defined above; and the adduct-intermediate of formula (4), is reacted with methyl hydrazine to produce the compound of formula (1a) ##STR38## wherein Ar is substituted phenyl and R.sup.2, R.sup.3 and R.sup.4 are as defined above.
- 5. A process of claim 4 wherein an acid addition salt of the reactant of formula (2) is used.
- 6. A process of claim 5 wherein the acid addition salt of the reactant of formula (2) is the hydroiodide or the methyl sulfate salt.
- 7. A process of claim 4 wherein a compound of formula (2a) ##STR39## wherein R.sup.8 and R.sup.9 are independently F or Cl, and R.sup.7 is lower alkyl, or an acid addition salt thereof, is reacted with an acid chloride of the formula (3b) ##STR40## wherein R.sup.2, R.sup.3 and R.sup.4 are independently H, CH.sub.3, Cl, or Br to produce the adduct-intermediate of formula (4b) ##STR41## wherein R.sup.2, R.sup.3, R.sup.4, R.sup.7, R.sup.8, and R.sup.9 are as defined above, and, with or without isolation of said adduct-intermediate of formula (4b), said adduct-intermediate is reacted with methyl hydrazine to produce the compound of formula (1b) ##STR42## wherein R.sup.2, R.sup.3, R.sup.4, R.sup.8, and R.sup.9 are as defined above.
- 8. A process of claim 7 wherein
- R.sup.7 is methyl, R.sup.8 is F, R.sup.9 is Cl, and
- (a) R.sup.2, R.sup.3, and R.sup.4 are each Cl;
- (b) R.sup.2 and R.sup.3 are each Br and R.sup.4 is H; or
- (c) R.sup.2 is CH.sub.3, R.sup.3 is Cl or Br, and R.sup.4 is H.
- 9. A process of claim 7 wherein the hydroiodide or methyl sulfate salt of a compound of formula (2b) ##STR43## is reacted with an acid chloride of the formula (3a) ##STR44## to produce the adduct-intermediate of formula (4c) ##STR45## and said adduct-intermediate is reacted with methyl hydrazine to produce the compound of formula (1c) ##STR46##
RELATED APPLICATION
This application claims priority from U.S. Provisional Patent Application Ser. No. 60/105,334, filed Oct. 23, 1998.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
6015826 |
Pechacek et al. |
Jan 2000 |
|