JPS6043349B2 - 1,2-diazepine compound with fused heterocycle - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel heterocyclic fused 1,2-diazepine derivative represented by general formula (I) and a method for producing the same.

(I) In the formula, A represents a fused pyridine, thiophene, or furan ring.

The compound represented by formula (I) of the present invention is a novel compound, has a central nervous system depressing effect, and is a compound useful as a pharmaceutical or an intermediate thereof.

Compound (I) of the present invention can be obtained by aminating a pyridine derivative having a condensed heterocycle represented by formula (■) with a suitable N-aminating agent such as an 0-aminosulfonic acid derivative,
A fused N-aminopyridine derivative of the heterocycle represented by the formula is prepared, and then this is reacted with an alkali to form the formula (
It can be produced by producing the ylide derivative represented by (2) and then irradiating it with light in an appropriate solvent. This reaction formula is shown below. During the ceremony,
A represents a fused pyridine, thiophene or furan ring. In producing the compound of the present invention, the above raw material compound (m) is dissolved in an organic solvent and reacted with an approximately equimolar amount of an N-aminating agent such as an O-aminosulfonic acid derivative. - The sulfonate salt (■) of an aminopyridine derivative is obtained in a yield of 90-95%.

When this salt is dissolved in water and made alkaline with sodium hydroxide, potassium carbonate, etc., crystals will precipitate. When this is removed and washed with water, an almost pure dimer (■-b) is obtained.
This dimer is in equilibrium with the ylide derivative represented by formula (■-a) in solution.

This dimer is stirred in a suitable solvent, irradiated with light using a high-pressure mercury lamp, and treated according to a conventional method to obtain the desired 1,2-diazepine derivative (1) with a condensed heterocycle. The solvent used during the light irradiation may be any solvent capable of dissolving the raw material dimer, but methylene chloride and acetone are preferred, and the most preferred are those to which 2 to 3% of glacial acetic acid is added. For substances that are difficult to form dimers, diazepine can be obtained by dissolving the sulfonate (■) in methanol and gradually adding a methanol solution of twice the molar amount of sodium hydroxide while irradiating with light. The light source may be a commonly used high-pressure mercury lamp, the intensity of which is appropriately selected depending on the amount of raw material used at the time. After the reaction is completed, the target compound is collected from the reaction mixture according to a conventional method.

For example, by using acetic acid-containing methylene chloride as a solvent, after the reaction is completed, acetic acid is extracted from the reaction solution with a weak alkaline aqueous solution such as a saturated sodium bicarbonate solution, washed with water, and then dried with a desiccant such as anhydrous sodium sulfate. . The target compound can be obtained by distilling off the solvent methylene chloride from this solution. The obtained target compound can be further subjected to recrystallization, column chromatography, etc. as necessary to obtain a pure product. Next, the present invention will be explained in more detail with reference to Examples.

Example 1 Pyrido[2.3-C]-1H-1.2-diazepine 1.
The dimer (2y) synthesized from 8-naphthyridine according to a general method was added to methylene chloride containing 2% glacial acetic acid (300ml).
) and irradiated with light for 5 hours by internal irradiation method using a 400W high-pressure mercury lamp while stirring.

The reaction solution was washed with aqueous sodium bicarbonate to remove glacial acetic acid, washed with water, dried, and then the solvent was distilled off. The resulting residue was subjected to alumina column chromatography, and the target compound was purified as a pure product from the methylene chloride eluate. Obtained. M. p. ll3~
114, red prismatic crystals (from isopropyl ether-benzene mixture) K. K♀Hnm (ε): 234 (19
000), 313 (2000), MSm/e:145(
M Tsunu? ■礪-1: 3250 (NH) δ (CDCl3): 5.84 (1H..dd), 6.5
8 (1H..d), 6.87 (1HNd), 7.02 (
1H,,d), 7.24 (1H1d), 8.09 (1H
．． ．． d), 7.3 (1H..br). Elemental analysis value C8H
7N3 calculated value: Cl66. l9; Hl4.86: Nl2
8.95 Actual value: Cl66. O6; Hl4.8l; Nl
28.93 Example 2 Pyrido[3.2-C]-1H-1.
A dimer (1.5 q) synthesized from 2-diazepine 1,5-naphthyridine according to a general method was irradiated with light in methylene chloride (300 mL) containing 2% glacial acetic acid under the same conditions as in Example 1. , to obtain 360 mg of the target compound.

M. p. 119-120, red needle crystals (from isopropyl ether-benzene mixture) λ=Ta,.

) Hnm (ε): 232 (16000), 306 (30
00), NSm/e: 145 (Mtsuν琵■礪-1:32
00(NH) δ(CDCl3): 6.18(1H.dd), 7.02
(1H,.d), 7.16 (1H..d), 6.8-7
．． 3 (2H,.m), 8.26 (1H..d), 6.6
(1H..br) Elemental analysis value C8H7N3 Calculated value: Cl66. l9; Hl4.86; Nl28.9
5 Actual value: Cl66. l8; Hl4.88; Nl28.
9O Example 3 Thieno[2,3-C]-1H-1,2-diazepine Mesitylene sulfonate synthesized from thieno[2,3-b]pyridine according to a general method (from which a dimer can be obtained) Dissolve 3.5y (difficult) in 350mL of methanol and add sodium hydroxide (1.3y
) was added dropwise in two drops in methanol (5 ml).

After further irradiation with light for 1.5 hours, the solvent was distilled off and the resulting residue was extracted with ether.The ether was distilled off from the extract, and the residue was subjected to alumina column chromatography. -1.1 da of the target compound was obtained from the hexane mixture eluate. M. p. 8l~83 solution, red needle crystals (from isopropyl ether) λ? ? Hnm(ε): 2
50 (11000), MSm/El5O (M ν Gourd ■C
m-1: 3200 (NH) δ (CDCl3): 5.98 (1H..dd), 6.6
7 (1H..d), 6.75 (1H..d), 6.8 (
1H. ．． br), 6.81 (1H1d), 6.94 (1
H. sd). Elemental analysis value C7H6N2S Calculated value: Cl55.98; Hl4. O3;Nll8.6
5 Actual value: Cl56. Ol; Hl4. O2;Nll8.
58 Example 4 Thieno[3,2-c]-1H-1,2-diazepine Mesitylene sulfonate (3.5y) obtained from thieno[3,2-b]pyridine was prepared in the same manner as in Example 3. After irradiation with light, the same treatment was performed to obtain 950 mg of the target compound.

M. p. 94-95 g, red needles (from isopropyl ether) λ2? Hnrrl. (ε):277(100
00), NSm/e: 150 (M ν Gourd Nc!n-1:
3250 (NH) δ (CDCl3): 5.92 (1H..dd), 6.4
2 (1H,.d), 6.6 (1H..br), 6.68
(1H,.d), 6.83 (1H1d), 7.28 (1
H. ．． d) Elemental analysis value C7H6N2S Calculated value: Cl55.98; Hl4. O3;Nl8.65
Actual value: Cl55.9l; Hl4. OO;Nll8.6
2 Example 5 Mesitylene sulfonate (3.34y) obtained from Furo[2,3-c]-1H-1,2-diazepine Furo[2,3-b]pyridine was treated under the same conditions as in Example 3. Approximately 600 m9 of the target compound was irradiated with light and treated in the same manner.
I got it.

Red viscous liquid and unstable λ2? Hnwl, (ε): 255. MSm/e:134
(M ν♀?o-1:3250(NH)δ(CJ)6)
:5.28 (1H..dd), 5.70 (1H,.d)
, 5.99 (1H..d), 6.4 (1H..br),
6.46 (2H1m) Elemental analysis value C7H6N2O

Claims (1)

[Claims] 1 General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, A
is a fused pyridine, thiophene or furan ring). 2 General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (II) (In the formula, A represents a fused pyridine, thiophene or furan ring) A general formula characterized by light irradiation (
I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, A is as above) A method for producing a 1,2-diazepine derivative with a condensed heterocycle.