Method for making pyrazolo[1,5-c]quinazoline derivatives and related compounds

Claim 1

A method for preparing compounds havng the structure ##STR537## wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy, and trifluoromethyl, or ##STR538## R 2 is selected from the group consisting of ##STR539## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy, and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR540## R 3 is selected from the group consisting of hydrogen, lower alkyl, benzyl, phenyl, or phenyl having a single substituent selected from the group consisting of lower alkoxy and trifluoromethyl; R 4 and R 5 are the same or different and are selected from the group consisting of hydrogen, alkyl of 1 to 4 carbons, alkoxy of 1 to 4 carbons, lower alkanoyloxy of 1 to 4 carbons, nitro, benzyloxy, benzyloxy having a single mono-lower alkoxy substituent, halogen, hydroxy, and trifluoromethyl; R 7 and R 8 may be the same or different and are selected from the group consisting of hydrogen, alkyl having 1 to 3 carbons, phenyl, phenyl having a mono-lower alkoxy substituent, benzyl, or benzyl having a mono-lower alkoxy substituent, or R 7 and R 8 taken together is a single cycloalkyl ring of 3 to 7 carbons; (CH 2 ) m and (CH 2 ) n represent straight or branched chain alkylene radicals, m and n are integers which may be the same of different and are 0 to 10, with the proviso that m+n is ≦10, and where m is 0, (CH 2 ) m represents a single bond, or where n is 0, (CH 2 ) n represents a single bond; and physiologically acceptable salts thereof, which comprises the steps of reacting a compound of the structure ##STR541## with an acetylenic compound of the structure R.sup.1 --C.tbd.C--R.sup.2 wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy, and trifluoromethyl, or ##STR542## R 2 is selected from the group consisting of ##STR543## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy, and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR544##

Claim 2

A method for preparing compounds havng the structure ##STR537## wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy, and trifluoromethyl, or ##STR538## R 2 is selected from the group consisting of ##STR539## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy, and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR540## R 3 is selected from the group consisting of hydrogen, lower alkyl, benzyl, phenyl, or phenyl having a single substituent selected from the group consisting of lower alkoxy and trifluoromethyl; R 4 and R 5 are the same or different and are selected from the group consisting of hydrogen, alkyl of 1 to 4 carbons, alkoxy of 1 to 4 carbons, lower alkanoyloxy of 1 to 4 carbons, nitro, benzyloxy, benzyloxy having a single mono-lower alkoxy substituent, halogen, hydroxy, and trifluoromethyl; R 7 and R 8 may be the same or different and are selected from the group consisting of hydrogen, alkyl having 1 to 3 carbons, phenyl, phenyl having a mono-lower alkoxy substituent, benzyl, or benzyl having a mono-lower alkoxy substituent, or R 7 and R 8 taken together is a single cycloalkyl ring of 3 to 7 carbons; (CH 2 ) m and (CH 2 ) n represent straight or branched chain alkylene radicals, m and n are integers which may be the same of different and are 0 to 10, with the proviso that m+n is ≦10, and where m is 0, (CH 2 ) m represents a single bond, or where n is 0, (CH 2 ) n represents a single bond; and physiologically acceptable salts thereof, which comprises the steps of reacting a compound of the structure ##STR541## with an acetylenic compound of the structure R.sup.1 --C.tbd.C--R.sup.2 wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy, and trifluoromethyl, or ##STR542## R 2 is selected from the group consisting of ##STR543## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy, and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR544##

Claim 3

A method for preparing compounds having the structure ##STR545## wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, or ##STR546## R 2 is selected from the group consisting of ##STR547## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR548## is R 6 is alkanoyl; R 3 is selected from the group consisting of hydrogen, lower alkyl, benzyl, phenyl, or phenyl having a single substituent selected from the group consisting of lower alkoxy and trifluoromethyl; R 4 and R 5 are the same or different and are selected from the group consisting of hydrogen, alkyl of 1 to 4 carbons, alkoxy of 1 to 4 carbons, lower alkanoyloxy of 1 to 4 carbons, nitro, benzyloxy, benzyloxy having a single mono-lower alkoxy substituent, halogen, hydroxy, and trifluoromethyl; R 7 and R 8 may be the same or different and are selected from the group consisting of hydrogen, alkyl having 1 to 3 carbons, phenyl, phenyl having a mono-lower alkoxy substituent, benzyl, or benzyl having a mono-lower alkoxy substituent, or R 7 and R 8 taken together is a single cycloalkyl ring of 3 to 7 carbons; (CH 2 ) m and (CH 2 ) n represent straight or branched chain alkylene radicals, m and n are integers which may be the same or different and are 0 to 10, with the proviso that m+n≦10, and where n is O, (CH 2 ) m represents a single bond, or where n is O, (CH 2 ) n represents a single bond, and physiologically acceptable salts thereof, which comprises the steps of reacting a compound of the structure ##STR549## with an acetylenic compound of the structure R.sup.1 --C.tbd.C--R.sup.2 wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy or trifluoromethyl; or ##STR550## R 2 is selected from the group consisting of ##STR551## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR552## and thereafter reacting the resulting compound with a compound of the structure ##STR553## wherein W is halogen, ##STR554## or hydroxy, and R 9 is hydrogen, or lower alkyl, to form the corresponding alkanoyl ester.

Claim 4

A method for preparing compounds having the structure ##STR545## wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, or ##STR546## R 2 is selected from the group consisting of ##STR547## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR548## is R 6 is alkanoyl; R 3 is selected from the group consisting of hydrogen, lower alkyl, benzyl, phenyl, or phenyl having a single substituent selected from the group consisting of lower alkoxy and trifluoromethyl; R 4 and R 5 are the same or different and are selected from the group consisting of hydrogen, alkyl of 1 to 4 carbons, alkoxy of 1 to 4 carbons, lower alkanoyloxy of 1 to 4 carbons, nitro, benzyloxy, benzyloxy having a single mono-lower alkoxy substituent, halogen, hydroxy, and trifluoromethyl; R 7 and R 8 may be the same or different and are selected from the group consisting of hydrogen, alkyl having 1 to 3 carbons, phenyl, phenyl having a mono-lower alkoxy substituent, benzyl, or benzyl having a mono-lower alkoxy substituent, or R 7 and R 8 taken together is a single cycloalkyl ring of 3 to 7 carbons; (CH 2 ) m and (CH 2 ) n represent straight or branched chain alkylene radicals, m and n are integers which may be the same or different and are 0 to 10, with the proviso that m+n≦10, and where n is O, (CH 2 ) m represents a single bond, or where n is O, (CH 2 ) n represents a single bond, and physiologically acceptable salts thereof, which comprises the steps of reacting a compound of the structure ##STR549## with an acetylenic compound of the structure R.sup.1 --C.tbd.C--R.sup.2 wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy or trifluoromethyl; or ##STR550## R 2 is selected from the group consisting of ##STR551## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR552## and thereafter reacting the resulting compound with a compound of the structure ##STR553## wherein W is halogen, ##STR554## or hydroxy, and R 9 is hydrogen, or lower alkyl, to form the corresponding alkanoyl ester.

Claim 5

A method for preparing compounds having the structure ##STR555## wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl; or ##STR556## R 2 is selected from the group consisting of ##STR557## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR558## R 6 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbons, mono-halophenyl, mono-lower alkoxy phenyl, phenylalkyl having 1 to 8 carbons in the alkyl group, phenyl or phenyl having a mono-lower alkoxy substituent; R 3 is selected from the group consisting of hydrogen, lower alkyl, benzyl, phenyl, or phenyl having a single substituent selected from the group consisting of lower alkoxy and trifluoromethyl; R 4 and R 5 are the same or different and are selected from the group consisting of hydrogen, alkyl of 1 to 4 carbons, alkoxy of 1 to 4 carbons, lower alkanoyloxy of 1 to 4 carbons, nitro, benzyloxy, benzyloxy having a single mono-lower alkoxy substituent, halogen, hydroxy, and trifluoromethyl; R 7 and R 8 may be the same or different and are selected from the group consisting of hydrogen, alkyl having 1 to 3 carbons, phenyl, phenyl having a lower alkoxy substituent, benzyl, or benzyl having a mono-lower alkoxy substituent, or R 7 and R 8 taken together is a single cycloalkyl ring of 3 to 7 carbons; (CH 2 ) m and (CH 2 ) n represent straight or branched chain alkylene radicals, m and n are integers which may be the same or different and are 0 to 10, with the proviso that m+n is ≦10, and where m is 0, (CH 2 ) m represents a single bond or where n is 0, (CH 2 ) n represents a single bond, and physiologically acceptable salts thereof, which comprises the steps of reacting a compound of the structure ##STR559## with an acetylene compound of the structure R.sup.1 --C.tbd.C--R.sup.2 wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl; or ##STR560## R 2 is selected from the group consisting of ##STR561## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR562## and then reacting the resulting alcohol with an acylating, agent to form the corresponding alkanoyl or phenyl-loweralkanoyl derivatives, or with an alkylating agent, phenylalkylating agent or phenylating agent to form the corresponding lower alkyl, phenyl-lower alkyl or phenyl ethers.

Claim 6

A method for preparing compounds having the structure ##STR555## wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl; or ##STR556## R 2 is selected from the group consisting of ##STR557## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR558## R 6 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbons, mono-halophenyl, mono-lower alkoxy phenyl, phenylalkyl having 1 to 8 carbons in the alkyl group, phenyl or phenyl having a mono-lower alkoxy substituent; R 3 is selected from the group consisting of hydrogen, lower alkyl, benzyl, phenyl, or phenyl having a single substituent selected from the group consisting of lower alkoxy and trifluoromethyl; R 4 and R 5 are the same or different and are selected from the group consisting of hydrogen, alkyl of 1 to 4 carbons, alkoxy of 1 to 4 carbons, lower alkanoyloxy of 1 to 4 carbons, nitro, benzyloxy, benzyloxy having a single mono-lower alkoxy substituent, halogen, hydroxy, and trifluoromethyl; R 7 and R 8 may be the same or different and are selected from the group consisting of hydrogen, alkyl having 1 to 3 carbons, phenyl, phenyl having a lower alkoxy substituent, benzyl, or benzyl having a mono-lower alkoxy substituent, or R 7 and R 8 taken together is a single cycloalkyl ring of 3 to 7 carbons; (CH 2 ) m and (CH 2 ) n represent straight or branched chain alkylene radicals, m and n are integers which may be the same or different and are 0 to 10, with the proviso that m+n is ≦10, and where m is 0, (CH 2 ) m represents a single bond or where n is 0, (CH 2 ) n represents a single bond, and physiologically acceptable salts thereof, which comprises the steps of reacting a compound of the structure ##STR559## with an acetylene compound of the structure R.sup.1 --C.tbd.C--R.sup.2 wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl; or ##STR560## R 2 is selected from the group consisting of ##STR561## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR562## and then reacting the resulting alcohol with an acylating, agent to form the corresponding alkanoyl or phenyl-loweralkanoyl derivatives, or with an alkylating agent, phenylalkylating agent or phenylating agent to form the corresponding lower alkyl, phenyl-lower alkyl or phenyl ethers.

Claim 7

A method for preparing compounds having the structure ##STR563## wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl; or ##STR564## R 2 is selected from the group consisting of ##STR565## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR566## R 6 is lower alkanoyl, phenyl-lower alkanoyl, benzoyl, alkyl of 1 to 4 carbons, phenyl-lower alkyl, or phenyl or phenyl having a mono-lower alkoxy substituent; R 3 is selected from the group consisting of hydrogen, lower alkyl, benzyl, phenyl, or phenyl having a single substituent selected from the group consisting of lower alkoxy and trifluoromethyl; R 4 and R 5 are the same or different and are selected from the group consisting of hydrogen, alkyl of 1 to 4 carbons, alkoxy of 1 to 4 carbons, lower alkanoyloxy of 1 to 4 carbons, nitro, benzyloxy, benzyloxy having a single mono-lower alkoxy substituent, halogen, hydroxy, and trifluoromethyl; R 7 and R 8 may be the same or different and are selected from the group consisting of hydrogen, alkyl containing 1 to 3 carbons, phenyl, phenyl having a mono-lower alkoxy substituent, benzyl, or benzyl having a mono-lower alkoxy substituent, or R 7 and R 8 taken together is a single cycloalkyl ring of 3 to 7 carbons; (CH 2 ) m and (CH 2 ) n represent straight or branched chain alkylene radicals, m and n are integers which may be the same of different and are 0 to 10, with the proviso that m+n is ≦10, and where m is O, (CH 2 ) m represents a single bond, or where n is O, (CH 2 ) n represents a single bond, and physiologically acceptable salts thereof, which comprises the steps of reacting a compound of the structure ##STR567## with an acetylene compound of the structure R.sup.1 --C.tbd.C--R.sup.2 wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl; or ##STR568## R 2 is selected from the group consisting of ##STR569## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR570## R 6 is lower alkanoyl, phenyl-lower alkanoyl, benzoyl, alkyl of 1 to 4 carbons, phenyl-lower alkyl, or phenyl or phenyl having a mono-lower alkoxy substituent.

Claim 8

A method for preparing compounds having the structure ##STR563## wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl; or ##STR564## R 2 is selected from the group consisting of ##STR565## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR566## R 6 is lower alkanoyl, phenyl-lower alkanoyl, benzoyl, alkyl of 1 to 4 carbons, phenyl-lower alkyl, or phenyl or phenyl having a mono-lower alkoxy substituent; R 3 is selected from the group consisting of hydrogen, lower alkyl, benzyl, phenyl, or phenyl having a single substituent selected from the group consisting of lower alkoxy and trifluoromethyl; R 4 and R 5 are the same or different and are selected from the group consisting of hydrogen, alkyl of 1 to 4 carbons, alkoxy of 1 to 4 carbons, lower alkanoyloxy of 1 to 4 carbons, nitro, benzyloxy, benzyloxy having a single mono-lower alkoxy substituent, halogen, hydroxy, and trifluoromethyl; R 7 and R 8 may be the same or different and are selected from the group consisting of hydrogen, alkyl containing 1 to 3 carbons, phenyl, phenyl having a mono-lower alkoxy substituent, benzyl, or benzyl having a mono-lower alkoxy substituent, or R 7 and R 8 taken together is a single cycloalkyl ring of 3 to 7 carbons; (CH 2 ) m and (CH 2 ) n represent straight or branched chain alkylene radicals, m and n are integers which may be the same of different and are 0 to 10, with the proviso that m+n is ≦10, and where m is O, (CH 2 ) m represents a single bond, or where n is O, (CH 2 ) n represents a single bond, and physiologically acceptable salts thereof, which comprises the steps of reacting a compound of the structure ##STR567## with an acetylene compound of the structure R.sup.1 --C.tbd.C--R.sup.2 wherein R 1 and R 2 are the same or different, and R 1 is selected from the group consisting of hydrogen, lower alkyl, phenyl, phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl; or ##STR568## R 2 is selected from the group consisting of ##STR569## hydrogen, lower alkyl, phenyl or phenyl having a single substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, with the proviso that at least one of R 1 and R 2 is ##STR570## R 6 is lower alkanoyl, phenyl-lower alkanoyl, benzoyl, alkyl of 1 to 4 carbons, phenyl-lower alkyl, or phenyl or phenyl having a mono-lower alkoxy substituent.