Process for production of pyrazole compounds
As a method capable of conveniently producing a pyrazole compound in a high yield, which is useful as a synthetic intermediate for a pharmaceutical agent such as a therapeutic agent for diabetes and the like, a production method of a compound represented by the formula (I) wherein n is an integer of 1 to 4 and R 1 is a. hydrocarbon group optionally having substituents, or a salt thereof, is provided, which includes reacting a compound represented by the formula, (II) wherein Q is a hydroxy group optionally having substituents or an amino group optionally having substituents, R is a hydrocarbon group optionally having substituents and other symbols are as defined above, or a salt thereof, with hydrazine or a salt thereof.
1 . A production method of a compound represented by the formula (I)
wherein n is an integer of 1 to 4 and R 1 is a hydrocarbon group optionally having substituents, or a salt thereof, which comprises reacting a compound represented by the formula (II)
wherein Q is a hydroxy group optionally having substituents or an amino group optionally having substituents, R is a hydrocarbon group optionally having substituents and other symbols are as defined above, or a salt thereof with hydrazine or a salt thereof:
2 . The production method of claim 1 , wherein Q is a hydroxy group.
3 . The production method of claim 1 , wherein n is 2.
4 . The production method of claim 1 , wherein the hydrocarbon group optionally having substituents for R or R 1 is an alkyl group having 1 to 8 carbon atoms.
5 . A compound represented by the formula (I)
wherein n is an integer of 1 to 4 and R 1 is a hydrocarbon group optionally having substituents, or a salt thereof.
6 . A production method of a compound represented by the formula (III)
wherein Z is an acyl group, n is an integer of 1 to 4 and R 1 is a hydrocarbon group optionally having substituents, or a salt thereof, which comprises subjecting a compound represented by the formula (I)
wherein the symbols in the formula are as defined above, or a salt thereof to an acylation reaction.
7 . A compound represented by the formula (III)
wherein Z is an acyl group, n is an integer of 1 to 4 and R 1 is a hydrocarbon group optionally having substituents, or a salt thereof.
8 . A production method of a compound represented by the formula (IV)
wherein R 3 is an alkyl group, Z is an acyl group, n is an integer of 1 to 4 and R 1 is a hydrocarbon group optionally having substituents, or a salt thereof, which comprises subjecting a compound represented by the formula (III)
wherein the symbols in the formula are as defined above, or a salt thereof to an alkylation reaction.
9 . A compound represented by the formula (IV)
wherein Z is an acyl group, n is an integer of 1 to 4, R 1 is a hydrocarbon group optionally having substituents and R 3 is an alkyl group, or a salt thereof.
10 . A production method of a compound represented by the formula (V)
wherein n is an integer of 1 to 4, R 1 is a hydrocarbon group optionally having substituents and R 3 is an alkyl group, or a salt thereof, which comprises subjecting a compound represented by the formula (IV)
wherein Z is an acyl group and other symbols are as defined above, or a salt thereof to a deacylation reaction.
11 . A production method of a compound represented by the formula (VII)
wherein R 4 is a hydrocarbon group optionally having substituents or a heterocyclic group optionally having substituents,
X is a bond, an oxygen atom, a sulfur atom, —CO—, —CS—, —CR 5 (OR 6 )— or —NR 7 — wherein R 5 and R 7 are each a hydrogen atom or a hydrocarbon group optionally having substituents, R 6 is a hydrogen atom or a hydroxyl-protecting group;
q is an integer of 0 to 3;
Y is an oxygen atom, a sulfur atom, —SO—, —SO 2 —, —NR 8 —, —CONR 8 — or —NR 8 CO— wherein R 8 is a hydrogen atom or a hydrocarbon group optionally having substituents;
ring A is an aromatic ring optionally further having 1 to 3 substituents;
r is an integer of 1 to 8;
R 3 is an alkyl group;
n is an integer of 1 to 4; and
R 0 is a hydrogen atom or a hydrocarbon group optionally having substituents, or a salt thereof, which comprises reacting a compound represented by the formula (II)
wherein Q is a hydroxy group optionally having substituents or an amino group optionally having substituents, and R and R 1 are the same or different and each is a hydrocarbon group optionally having substituents, or a salt thereof with hydrazine or a salt thereof to give a compound represented by the formula (I)
wherein the symbols in the formula are as defined above, or a salt thereof, subjecting the compound or a salt thereof to an acylation reaction to give a compound represented by the formula (III)
wherein Z is an acyl group and other symbols are as defined above, or a salt thereof, subjecting the compound or a salt thereof to an alkylation reaction to give a compound represented by the formula (IV)
wherein the symbols in the formula are as defined above, or a salt thereof, subjecting the compound or a salt thereof to a deacylation reaction to give a compound represented by the formula (V)
wherein the symbols in the formula are as defined above, or a salt thereof, reacting the compound or a salt thereof with a compound represented by the formula (VI)
wherein T is a leaving group and other symbols are as defined above, or a salt thereof, and conducting a hydrolysis reaction where necessary.
12 . A production method of a compound represented by the formula (VII)
wherein R 4 is a hydrocarbon group optionally having substituents or a heterocyclic group optionally having substituents,
X is a bond, an oxygen atom, a sulfur atom, —CO—, —CS—, —CR 5 (OR 6 )— or —NR 7 — wherein R 5 and R 7 are each a hydrogen atom or a hydrocarbon group optionally having substituents, R 6 is a hydrogen atom or a hydroxyl-protecting group;
q is an integer of 0 to 3;
Y is an oxygen atom, a sulfur atom, —SO—, —SO 2 —, —NR 8 —, —CONR 8 — or —NR 8 CO— wherein R 8 is a hydrogen atom or a hydrocarbon group optionally having substituents;
ring A is an aromatic ring optionally further having 1 to 3 substituents;
r is an integer of 1 to 8;
R 3 is an alkyl group;
n is an integer of 1 to 4;
R 0 is a hydrogen atom or a hydrocarbon group optionally having substituents, or a salt thereof, which comprises reacting a compound represented by the formula (II)
wherein Q is a hydroxy group optionally having substituents or an amino group optionally having substituents, and R and R 1 are the same or different and each is a hydrocarbon group optionally having substituents, or a salt thereof, with hydrazine or a salt thereof to give a compound represented by the formula (I)
wherein the symbols in the formula are as defined above, or a salt thereof, reacting the compound or a salt thereof with a compound represented by the formula (VI)
wherein T is a leaving group and other symbols are as defined above, or a salt thereof to give a compound represented by the formula (VIII)
wherein the symbols in the formula are as defined above, or a salt thereof, subjecting the compound or a salt thereof to an alkylation reaction, and conducting a hydrolysis reaction where necessary.