Asymmetrical Si rhodamine and rhodol synthesis

Patent metadata

Field	Value
Publication number	US-9714260-B2
Application number	US-201414759306-A
Country	US
Kind code	B2
Filing date	Jan 7, 2014
Priority date	Jan 7, 2013
Publication date	Jul 25, 2017
Grant date	Jul 25, 2017

Abstract

[Problem] To provide: a compound resulting from substituting with a silicon atom the oxygen atom at position 10 of a xanthene ring site of a rhodamine of which amino groups at position 3 and position 6 have an asymmetrical structure; a method for producing the compound; and a fluorescent probe that uses the compound.
[Solution] The compound represented by general formula (I) or a salt thereof.

First claim

The invention claimed is:

1. A compound of formula (I) below or a salt thereof

where:
R 1 is a hydrogen atom or 1-4 of the same or different monovalent substituents present on a benzene ring;
R 2 is a monovalent substituent;
R 3 and R 4 are, each independently, a hydrogen atom, C 1-6 alkyl group, or halogen atom;
R 5 and R 6 are, each independently, a C 1-6 alkyl group or aryl group;
R 7 and R 8 are, each independently, a hydrogen atom, C 1-6 alkyl group, or halogen atom;
R 9 and R 10 are, each independently, a hydrogen atom, C 1-6 alkyl group, or monovalent substituent cleaved by contact with a measured substance;
R 9 or R 10 optionally forms, together with R 3 or R 7 , a 5-7-member heterocyclyl or heteroaryl containing a nitrogen atom to which R 9 or R 10 binds, and optionally contains 1-3 additional heteroatoms selected from the group consisting of oxygen atoms, nitrogen atoms, and sulfur atoms as ring-constituting members; the heterocyclyl or heteroaryl optionally being substituted by a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aralkyl, or C 6-10 alkyl-substituted alkenyl group;
Y is selected from
(1) NR 11 R 12
(2) OR 13 or
(3) —N═N—R 14
where:
R 11 is a hydrogen atom, C 1-6 alkyl group, or monovalent substituent cleaved by contact with a measured substance;
R 12 is a hydrogen atom, C 1-6 alkyl group, or acyl group;
R 11 and R 12 optionally form a 5-7-member heterocyclyl containing a nitrogen atom to which R 11 and R 12 bind, and optionally contain 1-3 additional heteroatoms selected from the group consisting of oxygen atoms, nitrogen atoms, and sulfur atoms as ring-constituting members; the heterocyclyl optionally being substituted by a C 1-6 alkyl group;
R 13 is a hydrogen atom or monovalent substituent cleaved by contact with a measured substance; and
R 14 is an aryl group; and
X is a silicon, germanium, or tin atom;
when Y is —NR 11 R 12 , (i) R 9 and R 10 are not monovalent substituents cleaved by contact with a measured substance, and (ii) at least one of R 9 and R 10 differs from at least one of R 11 and R 12 ; provided that a compound wherein R 9 and R 10 are hydrogen, R 12 is a hydrogen, and R 11 is a monovalent substituent cleaved by contact with a measured substance, is excluded;
when Y is —OR 13 and R 13 is a hydrogen atom, R 9 or R 10 is optionally a monovalent substituent cleaved by contact with a measured substance; and
when Y is —N═N—R 14 , R 9 and R 10 are not a monovalent substituent cleaved by contact with a measured substance.

2. The compound or salt thereof according to claim 1 having the structure of formula (Ia) below, Y being —NR 11 R 12

where:
R 1 to R 12 and X are as defined in formula (I), but (i) R 9 and R 10 are not monovalent substituents cleaved by contact with a measured substance, and (ii) when R 11 and R 12 are hydrogen atoms, R 9 and R 10 are not both hydrogen atoms.

3. The compound or salt thereof according to claim 2 , wherein R 9 or R 10 forms, together with R 3 or R 7 , a 5-7-member heterocyclyl or heteroaryl containing a nitrogen atom to which R 9 or R 10 binds; wherein the heterocyclyl or heteroaryl optionally contains 1-3 additional heteroatoms selected from the group consisting of oxygen atoms, nitrogen atoms, and sulfur atoms as ring-constituting members; the heterocyclyl or heteroaryl optionally being substituted by a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aralkyl group, or C 6-10 alkyl-substituted alkenyl group.

4. The compound or salt thereof according to claim 3 , wherein R 9 forms, together with R 3 , a 5-7-member heterocyclyl or heteroaryl containing a nitrogen atom to which R 9 binds.

5. The compound or salt thereof according to claim 4 , having the structure of formula (Ia-1) below

where R 1 -R 2 , R 4 -R 8 , R 10 -R 12 , and X are as defined in formula (Ia).

6. The compound or salt thereof according to claim 2 , wherein R 11 and R 12 form a 5-7-member heterocyclyl containing a nitrogen atom to which R 11 and R 12 bind; wherein the heterocyclyl optionally contains 1-3 additional heteroatoms selected from the group consisting of oxygen atoms, nitrogen atoms, and sulfur atoms as ring-constituting members; the heterocyclyl optionally being substituted by a C 1-6 alkyl group.

7. A compound of formula (Ia) below or a salt thereof

where:
R 1 is a hydrogen atom or 1-4 of the same or different monovalent substituents present on a benzene ring;
R 2 is a monovalent substituent;
R 3 and R 4 are, each independently, a hydrogen atom, C 1-6 alkyl group, or halogen atom;
R 5 and R 6 are, each independently, a C 1-6 alkyl group or aryl group;
R 7 and R 8 are, each independently, a hydrogen atom, C 1-6 alkyl group, or halogen atom;
R 9 and R 10 are, each independently, a hydrogen atom, C 1-6 alkyl group, or monovalent substituent cleaved by contact with a measured substance;
R 9 or R 10 optionally forms, together with R 3 or R 7 , a 5-7-member heterocyclyl or heteroaryl containing a nitrogen atom to which R 9 or R 10 binds, and optionally contains 1-3 additional heteroatoms selected from the group consisting of oxygen atoms, nitrogen atoms, and sulfur atoms as ring-constituting members; the heterocyclyl or heteroaryl optionally being substituted by a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aralkyl, or C 6-10 alkyl-substituted alkenyl group;
X is a silicon, germanium, or tin atom;
R 9 and R 10 are not monovalent substituents cleaved by contact with a measured substance; and
R 11 and R 12 form a piperazine ring together with a nitrogen atom to which R 11 and R 12 bind.

8. The compound or salt thereof according to claim 7 , having the structure of formula (Ia-2) below

where R 1 -R 10 and X are as defined in formula (Ia), and R 15 is a C 1-6 alkyl group.

9. A compound of formula (I) below or a salt thereof

where:
R 1 is a hydrogen atom or 1-4 of the same or different monovalent substituents present on a benzene ring;
R 2 is a monovalent substituent;
R 3 and R 4 are, each independently, a hydrogen atom, C 1-6 alkyl group, or halogen atom;
R 5 and R 6 are, each independently, a C 1-6 alkyl group or aryl group;
R 7 and R 8 are, each independently, a hydrogen atom, C 1-6 alkyl group, or halogen atom;
R 9 and R 10 are, each independently, a hydrogen atom, C 1-6 alkyl group, or monovalent substituent cleaved by contact with a measured substance;
R 9 or R 10 optionally forms, together with R 3 or R 7 , a 5-7-member heterocyclyl or heteroaryl containing a nitrogen atom to which R 9 or R 10 binds, and optionally contains 1-3 additional heteroatoms selected from the group consisting of oxygen atoms, nitrogen atoms, and sulfur atoms as rin

Assignees

• Univ Tokyo

Inventors

• Nagano Tetsuo
• Hanaoka Kenjiro
• Egawa Takahiro
• KUSHIDA Yu
• NUMASAWA Koji
• MYOCHIN Takuya
• PIAO Wen

Classifications

• C09B69/008

  Dyes containing a substituent, which contains a silicium atom · CPC title

• C09B11/28

  Pyronines {; Xanthon, thioxanthon, selenoxanthan, telluroxanthon dyes} · CPC title

• C07C213/08

  by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups · CPC title

• C07F7/0816 Primary

  said ring comprising Si as a ring atom · CPC title

• C07C209/68

  from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton · CPC title