A pyrrole compound having a substituted sulfonyl group at the 1-position (hereinafter to be referred to as a sulfonylpyrrole compound) is useful as an acid secretion inhibitor (proton pump inhibitor), a therapeutic drug for a neoplastic disease or an autoimmune disease (patent documents 1-3).
For example, patent document 2 describes, as a compound having an acid secretion suppressive activity, a compound represented by the formula:
wherein r1 is a monocyclic nitrogen-containing heterocyclic group optionally condensed with a benzene ring or a heterocycle, wherein the monocyclic nitrogen-containing heterocyclic group optionally condensed with a benzene ring or a heterocycle optionally has substituent(s), r2 is an optionally substituted C6-14 aryl group, an optionally substituted thienyl group or an optionally substituted pyridyl group, r3 and r4 are each a hydrogen atom, or one of r3 and r4 is a hydrogen atom and the other is an optionally substituted lower alkyl group, an acyl group, a halogen atom, a cyano group or a nitro group, and r5 is an alkyl group, or a salt thereof.
Patent document 2 describes, as a production method of a sulfonylpyrrole compound, the following method using a pyrrole-3-carboxylate:

Patent document 3 describes the following production method of a sulfonylpyrrole compound:
wherein Q is chlorine, bromine or iodine.
On the other hand, the following method is known as a production method of a 2-halogeno-3-cyanopyrrole compound.

As a method for producing a 3-cyanopyrrole compound from a 2-halogeno-3-cyanopyrrole compound, the following methods are known.

As a method for producing a 3-formylpyrrole compound from a 3-cyanopyrrole compound, the following methods are known.

In addition, as a 3-cyanopyrrole compound, the following compounds are known.

TABLE 1waxayazaRd3-CN4-Cl5-Cl2-(p-CF3O—C6H5)C2H54-NO22-Br3-Br5-(p-Cl—C6H5)C2H54-NO22-Cl3-Cl5-(3,4-diCl—C6H5)C2H54-NO22-Cl3-Cl5-(p-Br—C6H5)C2H53-CN4-Cl5-Cl2-(p-CF3—C6H5)C2H53-CN4-Cl5-Cl2-(3,4-diCl—C6H5)C2H53-CN4-Cl5-Cl2-(p-Cl—C6H5)C2H54-NO22-(p-Cl—C6H5)5-CF32-(p-Cl—C6H5)C2H53-CN4-Br5-Br2-BrC2H53-CN4-Br5-CF32-(p-Cl—C6H5)C2H53-CN4-Cl5-CF32-(p-Cl—C6H5)C2H54-NO23-(p-Cl—C6H5)5-CF32-(p-Cl—C6H5)C2H54-NO24-(3,4-diCl—C6H5)5-CF32-(p-Cl—C6H5)C2H54-NO23-(m-CN—C6H5)2-CF35-(p-Cl—C6H5)C2H53-CN4-Br5-Br2-(p-CF3—C6H5)C2H53-CN2-Cl4-Cl5-(3,4-diCl—C6H5)C2H53-CN2-Cl4-Br5-(p-Br—C6H5)C2H5


TABLE 2Compound NoQnxbybzb2-53-ClHCNH2-63-ClCH3CNH2-73-ClClCNH2-83-ClBrCNH2-313-ClHCNCH32-323-ClHCNCHO2-573-MeHCNH2-583-MeCH3CNH2-593-MeClCNH2-603-MeBrCNH2-723-MeHCNCH32-733-MeHCNCHO2-923-cyclopropylHCNH2-933-cyclopropylCH3CNH2-943-cyclopropylClCNH2-953-cyclopropylBrCNH2-1083-cyclopropylHCNCH32-1093-cyclopropylHCNCHO
TABLE 3Compound NoQnxbybzb2-1285-cyclopropylHCNH2-1295-cyclopropylCH3CNH2-1305-cyclopropylClCNH2-1315-cyclopropylBrCNH2-1455-cyclopropylHCNCH32-1465-cyclopropylHCNCHO2-1575-EtHCNH2-1585-EtCH3CNH2-1595-EtClCNH2-1605-EtBrCNH2-1755-EtHCNCH32-1765-EtHCNCHO2-1953-C≡CHHCNH2-1963-C≡CHCH3CNH2-1973-C≡CHClCNH2-1983-C≡CHBrCNH2-2123-C≡CHHCNCH32-2133-C≡CHHCNCHO
In addition, as a 2-mercaptopyrrole derivative, the following compounds are known.
For example, non-patent document 5 describes 2-mercaptopyrrole derivative (A) having a cyano group at the 3-position:
non-patent document 6 describes 2-mercaptopyrrole derivative (B) having a cyano group at the 3-position:
patent document 11 describes 2-mercaptopyrrole derivative (C) having a cyano group at the 3-position:
and patent document 12 describes 2-mercaptopyrrole derivative (D) having a cyano group at the 3-position:

As a synthesis method of these 2-mercaptopyrrole derivatives having a cyano group at the 3-position, non-patent document 5 describes, as shown in the following reaction scheme, a synthesis method of mercaptopyrrole derivative (A) by a reaction of a (2-oxoethyl) malononitrile derivative with hydrogen sulfide; however, a desulfurization reaction is not described.

In addition, non-patent document 6 describes, as shown in the following reaction scheme, a synthesis method of 2-mercaptopyrrole derivative (B) having a cyano group at the 3-position is described; however, it is not by a ring closure reaction of a (2-oxoethyl) malononitrile derivative and a sulfur compound. Furthermore, a desulfurization reaction of the obtained 2-mercaptopyrrole derivative is not described.

Moreover, patent document 11 describes, as shown in the following reaction scheme, a synthesis method of 2-mercaptopyrrole derivative (C) having a cyano group at the 3-position; however, it is not by a ring closure reaction of a (2-oxoethyl) malononitrile derivative and a sulfur compound. Furthermore, a desulfurization reaction of the obtained 2-mercaptopyrrole derivative is not described.

Moreover, patent document 12 describes, as shown in the following reaction scheme, a synthesis method of 2-mercaptopyrrole derivative (D) having a cyano group at the 3-position; however, it is not by a ring closure reaction of a (2-oxoethyl) malononitrile derivative and a sulfur compound. In addition, a desulfurization reaction of the obtained 2-mercaptopyrrole derivative is not described.

USPTO Backgrounds
USPTO Backgrounds