Pyrazolopyrimidine compound and a process for preparing the same

A compound which is

• 1-(3-ethoxybenzyl)-4-[4-[4-[2-(dimethylamino)ethoxy]benzoyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-[2-(1-piperidyl)ethoxy]benzoyl]piperazin-1-yl]-1H-pyrazolo-[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-(dimethylaminomethyl)benzoyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-(diethylaminomethyl)benzoyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-(1-pyrrolidinylmethyl)benzoyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-[N-(cyclopropylcarbonyl)-N-[2-(dimethylamino)ethyl]-amino]benzoyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-[N-[(2-methoxyethoxy)carbonyl]-N-[2-(dimethylamino)-ethyl]amino]benzoyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-[N-isobutyl-N-[2-(dimethylamino)ethyl]amino]benzoyl]-piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[(1-propylpiperidin-4-yl)carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[3-(1-isopropylpiperidin-4-yl)propionyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[[trans-4-(dimethylaminomethyl)cyclohexyl]carbonyl]-piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[[trans-4-(1-pyrrolidinyl)cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[(E)-3-(1-isopropylpiperidin-4-yl)acryloyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-[3-(dimethylamino)-2,2-dimethylpropyloxy]benzoyl]-piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-propylpyridin-2-yl)methyl]-4-[4-[4-[3-(dimethylamino)-2,2-dimethylpropyloxy]-benzoyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-[N-acetyl-N-[2-(1-pyrrolidinyl)ethyl]amino]benzoyl]-piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-[N-acetyl-N-[2-(dimethylamino)ethyl]amino]benzoyl]-piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-(ethylaminomethyl)benzoyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[(trans-4-piperidinocyclohexyl)carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[[trans-4-((3S)-3-hydroxy-1-pyrrolidinyl)cyclohexyl]carbonyl]-piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[[trans-4-[N-acetyl-N-[2-(dimethylamino)ethyl]amino]-cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[[trans-4-[N-(2-furoyl)-N-[2-(dimethylamino)ethyl]amino]-cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[[trans-4-[N-(crotonoyl)-N-[2-(dimethylamino)ethyl]amino]-cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[[trans-4-[N-(methylthiocarbamoyl)-N-[2-(dimethylamino)-ethyl]amino]cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(2-propyl-1,3-thiazol-4-yl)methyl]-4-[4-[4-[N-crotonoyl-N-[2-(dimethylamino)ethyl]-amino]-benzoyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-ethoxypyridin-2-yl)methyl]-4-[4-[[trans-4-(1-pyrrolidinyl)cyclohexyl]carbonyl]-piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-propylpyridin-2-yl)methyl]-4-[4-[[trans-4-(1-pyrrolidinyl)cyclohexyl]carbonyl]-piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-propylpyridin-2-yl)methyl]-4-[4-[[trans-4-(diethylaminomethyl)cyclohexyl]-carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-propylpyridin-2-yl)methyl]-4-[4-[[trans-4-[N-isopropyl-N-(2-methoxyethyl)amino-methyl]cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(2-propyl-1,3-thiazol-4-yl)methyl]-4-[4-[4-[2,2-dimethyl-3-(dimethylamino)propyloxy]benzoyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-propylpyridin-2-yl)methyl]-4-[4-[[trans-4-(dipropylamino)cyclohexyl]carbonyl]-piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(2-propyl-1,3-thiazol-4-yl)methyl]-4-[4-[[trans-4-(dipropylamino)cyclohexyl]-carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-propylpyridin-2-yl)methyl]-4-[4-[[trans-4-(1-piperidyl)cyclohexyl]carbonyl]-piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-ethoxypyridin-2-yl)methyl]-4-[4-[[trans-4-(1-piperidyl)cyclohexyl]carbonyl]-piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(2-propyl-1,3-thiazol-4-yl)methyl]-4-[4-[[trans-4-(1-piperidyl)cyclohexyl]-carbonyl]-piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[[trans-4-(ethylamino)cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo [3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[3-[2-(diisopropylamino)ethoxy]-4-[3-(dimethylamino)-2,2-(dimethyl)propyloxy]benzoyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-[N-(cyclopropanecarbonyl)-N-[2-(dimethylamino)ethyl]-amino]piperidinocarbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-(3,3-dimethylpiperadino)piperidinocarbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[4-[N-ethyl-N-[2-(dimethylamino)ethyl]amino]piperidino-carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-propylpyridin-2-yl)methyl]-4-[4-[[trans-4-[[N-(t-butyl)-N-ethylamino]methyl]cyclohexyl]-carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-propylpyridin-2-yl)methyl]-4-[4-[[trans-4-[[N-(t-butyl)-N-[2-(methoxy)ethyl]amino]-methyl]cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-ethoxypyridin-2-yl)methyl]-4-[4-[[trans-4-[[N-(t-butyl)-N-[2-(methoxy)ethyl]amino]-methyl]cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[[trans-4-[[N-(t-butyl)-N-[2-(methoxy)ethyl]amino]methyl]-cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(2-propyl-1,3-thiazol-4-yl)methyl]-4-[4-[[trans-4-[[N-(t-butyl)-N-[2-(methoxy)ethyl]amino]-methyl]cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[[trans-4-[[N-(t-butyl)-N-[2-(hydroxy)ethyl]amino]methyl]-cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-propylpyridin-2-yl)methyl]-4-[4-[[trans-4-[N-[2-(dimethylamino)ethyl]-N-(methane-sulfonyl)amino]cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-ethoxypyridin-2-yl)methyl]-4-[4-[[trans-4-[N-[2-(dimethylamino)ethyl]-N-(methanesulfonyl)amino]cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(2-propyl-1,3-thiazol-4-yl)methyl]-4-[4-[[trans-4-[N-[2-(dimethylamino)ethyl]-N-(methanesulfonyl)amino]cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-propylpyridin-2-yl)methyl]-4-[4-[[trans-4-[[N-[2-(dimethylamino)ethyl]-N-pivaloylamino]methyl]cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-[(6-propylpyridin-2-yl)methyl]-4-[4-[[trans-4-[[N-(cyclopropanecarbonyl)-N-[2-(dimethylamino)ethyl]amino]methyl]cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxybenzyl)-4-[4-[[trans-4-[N-[2-(dimethylamino)ethyl]-N-propionylamino]-cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxy-2-fluorobenzyl)-4-[4-[(trans-4-piperidin-1-ylcyclohexyl)carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxy-2-fluorobenzyl)-4-[4-[[trans-4-[[N-(t-butyl)-N-[2-(methoxy)ethyl]amino]-methyl]cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxy-2-fluorobenzyl)-4-[4-[4-(ethylaminomethyl)benzoyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• 1-(3-ethoxy-2-fluorobenzyl)-4-[4-[4-[N-acetyl-N-[2-(dimethylamino)ethyl]amino]benzoyl]-piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;
• or a pharmaceutically acceptable salt thereof.

A method for preparing a compound of the following formula [I-A]:

• wherein R1 is
• (A) a substituted aryl group,
• (B) an optionally substituted nitrogen-containing aliphatic heteromonocyclic group,
• (C) a substituted cyclo-lower alkyl group,
• (D) an optionally substituted amino group, or
• (E) a substituted heteroaryl group,
• R2 is (a) an optionally substituted heteroaryl group or (b) an optionally substituted aryl group,
• Y is a single bond, a lower alkylene group or a lower alkenylene group,
• Za is a group of the formula:
• —CO—, —SO2— or ═C═N—CN,
• Q is a lower alkylene group, and q is an integer of 0 or 1, which comprises reacting a compound of the formula [II]:
• wherein the symbols are the same as defined above or a salt thereof with a compound of the formula [III]:
• R1—(O)q—Y-Za—OR3 [III]
• wherein R□ is a hydrogen atom, a lower alkyl group or a benzyl group and other symbols are the same as defined above or a salt thereof.

A method for preparing a compound of the formula [I-B]:

• wherein R1 is
• (A) a substituted aryl group,
• (B) an optionally substituted nitrogen-containing aliphatic heteromonocyclic group,
• (C) a substituted cyclo-lower alkyl group,
• (D) an optionally substituted amino group, or
• (E) a substituted heteroaryl group,
• R2 is (a) an optionally substituted heteroaryl group or (b) an optionally substituted aryl group,
• Y is a single bond, a lower alkylene group or a lower alkenylene group,
• Q is a lower alkylene group, and q is an integer of 0 or 1, which comprises reacting a compound of the formula [II]:
• wherein the symbols are the same as defined above or a salt thereof with an aldehyde compound of the formula [IV]:
• R1—(O)q—Y—CHO [IV]
• wherein the symbols are the same as defined above.

A method for preparing a compound of the formula [I-C]:

• wherein R11 is an amino group optionally substituted by a group selected from a lower alkyl group, a (mono- or di-lower alkyl)amino-lower alkyl group and a nitrogen-containing aliphatic heteromonocyclic group-substituted lower alkyl group, Za is a group of the formula:
• —CO—, —SO2— or ═C═N—CN, R2 is (a) an optionally substituted heteroaryl group or (b) an optionally substituted aryl group, and Q is a lower alkylene group, which comprises reacting a carboxylic acid compound of the formula [V]:
• wherein the symbols are the same as defined above or a salt thereof with a compound of the formula [VI]:
• R11—H [VI]
• wherein R11 is the same as defined above or a salt thereof.

A method for preparing a compound of the formula [I-D]:

• wherein R12 is an optionally substituted nitrogen-containing aliphatic heteromonocyclic group or an optionally substituted amino group, R2 is (a) an optionally substituted heteroaryl group or (b) an optionally substituted aryl group, and Q is a lower alkylene group, which comprises reacting a compound of the formula [VII]:
• wherein W2 is a reactive residue and other symbols are the same as defined above with a compound of the formula [VIII]:
• wherein the symbol is the same as defined above or a salt thereof, or
• reacting a compound of the formula [II]:
• wherein the symbols are the same as defined above or a salt thereof with a compound of the formula [IX]:
• wherein the symbol is the same as defined above.