Hetero-fused cyclic compound

Patent metadata

Field	Value
Publication number	US-9975910-B2
Application number	US-201414904860-A
Country	US
Kind code	B2
Filing date	Jul 18, 2014
Priority date	Jul 23, 2013
Publication date	May 22, 2018
Grant date	May 22, 2018

Abstract

A compound represented by the formula (I) or a salt thereof:

wherein a ring Z is a 5 to 6-membered heteroaromatic ring having one or two heteroatoms in the ring; X 1 is a hydrogen atom, a hydroxy group, a hydroxy C 1-6 alkyl group, —B(OH) 2 , a boronate ester group, a cyclic boronate ester group, a boranyl group, a cyclic boranyl group, —BF 3 M n1 , —Sn(R 12 )(R 13 )(R 14 ), a leaving group, a carboxy group, a formyl group, or —NR 16 R 17 ; and X 2 is a hydrogen atom or —CO 2 R 18 .

First claim

The invention claimed is:

1. A compound represented by formula (I) or a salt thereof:

wherein the ring Z is a 6 membered heteroaromatic ring having one or two heteroatoms in the ring;
X 1 is —B(OH) 2 , a boronate ester group, a cyclic boronate ester group, -BF 3 M n1 wherein n1 is 0 or 1 and M is an alkali metal, —Sn(R 12 )(R 13 )(R 14 ) wherein R 12 , R 13 , and R 14 are the same or different and are a C 1-6 alkyl group, or -L wherein L is a halogen atom, a methanesulfonyloxy group, a p-toluenesulfonyloxy group, or a trifluoromethanesulfonyloxy group; and
X 2 is a hydrogen atom or —CO 2 R 18 wherein R 18 is a hydrogen atom, a C 1-6 alkyl group, or a protecting group for a carboxy group.

2. The compound or the salt thereof according to claim 1 , wherein the compound or the salt thereof is a compound represented by formula (III) or a salt thereof:

wherein the ring Z2 is a 6-membered heteroaromatic ring having one or two heteroatoms in the ring; and X 1 and X 2 are the same as defined as in claim 1 .

3. The compound represented by formula (III) or the salt thereof according to claim 2 , wherein the ring Z2 is a pyridine ring, a pyrazine ring, a pyrimidine ring, or a pyridazine ring.

4. The compound or the salt thereof according to claim 2 , wherein the fused ring consisting of the ring Z2 and the adjacent ring is a furo[3,4-b]pyridine ring, a furo[3,4-c]pyridine ring, a furo[3,4-b]pyrazine ring, a furo[3,4-d]pyrimidine ring, a furo[3,4-c]pyridazine ring, or a furo[3,4-d]pyridazine ring.

5. The compound or the salt thereof according to claim 1 , wherein the boronate ester group is a substituent represented by formula (Y-1) and the cyclic boronate ester group is a substituent represented by formulae (Y-2) to (Y-13)

wherein R 1 to R 9 are the same or different and are a C 1-6 alkyl group.

6. The compound or the salt thereof according to claim 1 , wherein the compound or the salt thereof is
1-bromo-5,7-dihydrofuro[3,4-d]pyridazine,
3-chloro-5,7-dihydrofuro[3,4-b]pyridine,
3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,7-dihydrofuro[3,4-b]pyridine,
3-(tributylstannyl)-5,7-dihydrofuro[3,4-b]pyridine,
6-bromo-1,3-dihydrofuro[3,4-c]pyridine,
2-chloro-5,7-dihydrofuro[3,4-d]pyrimidine,
2-(tributylstannyl)-5,7-dihydrofuro[3,4-d]pyrimidine,
2-chloro-5,7-dihydrofuro[3,4-b]pyrazine,
2-(tributylstannyl)-5,7-dihydrofuro[3,4-b]pyrazine,
potassium (5,7-dihydrofuro[3,4-b]pyridin-3-yl)trifluoroborate,
2-chloro-5,7-dihydrofuro[3,4-b]pyridine,
2-bromo-5,7-dihydrofuro[3,4-b]pyridine,
2-(tributylstannyl)-5,7-dihydrofuro[3,4-b]pyridine,
1-chloro-5,7-dihydrofuro[3,4-d]pyridazine, or
4-chloro-5,7-dihydrofuro[3,4-d]pyrimidine.

7. A method of producing a compound represented by formula (I) or salt thereof according to claim 1 :

the method comprising reacting a compound represented by formula (IV):

wherein R a1 to R a6 are the same or different and are a C 1-6 alkyl group;
with a compound represented by formula (V):

wherein Q 1 and Q 2 are each a leaving group, to form the compound represented by formula (I) or salt thereof.

Assignees

• Eisai R&D Man Co Ltd

Inventors

• Tanaka Keigo
• Fukuyama Takashi
• Murai Norio
• Itano Wataru
• Hirota Shinsuke
• Iida Daisuke
• Azuma Hiroshi

Classifications

• A61P31/10

  Antimycotics · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• C07F5/025

  Boronic and borinic acid compounds · CPC title

• C07D493/04

  Ortho-condensed systems · CPC title

• C07D513/04

  Ortho-condensed systems · CPC title