CH623053A5 - Processes for the preparation of new imidazobenzoxazines - Google Patents

Description

The present invention relates to processes for the preparation of new imidazobenzoxazines and their salts, said imidazobenzoxazines corresponding to the formula:

so ss

CD

65

in which X represents a hydrogen atom, a nitro radical, an amino radical, an alkanoylamino radical containing from 2 to 5 carbon atoms or a group of formula:

-NH-CO-COO-R '

in which R 'represents a hydrogen atom or an alkyl radical containing from 1 to 5 carbon atoms, Z represents a group of formula —COOR in which R represents a hydrogen atom, an alkyl radical containing from 1 to 5 atoms of carbon or a group of formula:

- (CH2) „- N

/

Ri

R2

25

in which n is equal to 1,2 or 3, Ri and R2, identical or different, represent a hydrogen atom or an alkyl radical containing from 1 to 5 carbon atoms, or Ri and R2 form together with the atom d nitrogen to which they are linked, a saturated heterocycle containing from 4 to 6 carbon atoms and which may, if desired, contain another heteroatom which may, if necessary, be substituted by an alkyl radical containing from 1 to 5 carbon atoms, or Z represents a group of formula:

Ri

30

-CO-N

\

R2

in which Ri and R2 have the meaning already indicated.

In formula I and in what follows, the term alkanoylamino containing from 2 to 5 carbon atoms denotes, for example, an acetamido, propionamido, butyramido radical, the term alkyl radical containing from 1 to 5 carbon atoms denotes, for example , a methyl, ethyl, propyl, isopropyl, butyl or pentyl radical, the expression saturated heterocycle containing from 4 to 6 carbon atoms and which may comprise another heteroatom which may be unsubstituted or substituted by an alkyl radical containing from 1 to 5 carbon atoms, denotes, for example, a pyrrolidino, piperidino, morpholino, piperazinyl, N-methyl-piperazinyl, N-ethyl-piperazinyl, N-propyl-piperazinyl or N-butyl-piperazinyl radical.

The products of formula I (with the exception of those in which Z represents a carboxyl group and / or X represents a group - NH-CO-COOH), have a basic character; in this case, the salts formed can be, for example, the salts formed with hydrochloric, hydrobromic, hydroiodic, nitric, sulfuric, phosphoric, acetic, formic, benzoic, maleic, fumaric, succinic, tartaric, citric acids. , oxalic, glyoxylic, aspartic, alkanesulfonic, such as methane sulfonic acid and aryl-sulfonic, such as benzene sulfonic acid.

The products of formula I in which Z represents a carboxyl group and / or X represents a free acid group such as the —NH — CO — COOH group have an acid character; in this case the salts may be metal salts or addition salts with nitrogenous bases.

The metal salts can be, for example, the salts of alkali metals, such as sodium, potassium or lithium, of alkaline earth metals, such as calcium, or of metals such as aluminum or magnesium.

The nitrogen base salts can be, for example, the salts

5

623053

ammonium or amine salts, such as tromethamine, lysine, arginine, triethanolamine.

Among the products obtained by the process, object of the invention

in which R3 represents an alkyl radical containing from 1 to 5 carbon atoms, to obtain a product of formula:

in which Ri and R2 have the above meaning.

Among the latter, there may be mentioned the derivatives corresponding to formula I above, as well as their salts, characterized in that in said formula I, X represents a hydrogen atom, a nitro radical, an acetamido radical or a group : —NH— CO — COO — R 'in which R' represents a hydrogen atom, a methyl or ethyl radical, Z represents a group —COOR in which R represents a hydrogen atom, a methyl, ethyl or morpholino radical ethyl or Z represents a 4-methyl-piperazin-1-yl carbonyl radical.

Among these, mention may finally be made of the derivatives corresponding to formula I above, as well as their salts, characterized in that in formula I, X represents a hydrogen atom, Z represents a carboxyl group, a morpho group -ino-ethoxy carbonyl or a 4-methyl-piperazin-1-yl carbonyl group.

Among the products obtained by the process which is the subject of the invention, there may be mentioned more particularly 8-nitro 4H-imidazo [2, l-c] [1,4] -benzoxazin-2-carboxylic acid and its salts.

The basic procedure for the preparation of products of formula I, as well as their salts, is characterized in that a product of formula is decarboxylated:

00H .COOR-

35

in which R3 has the meaning already indicated.

According to a second process, the product of formula IB is reduced, to obtain a product of formula:

COOR.

40 h2N

(IC)

in which R3 has the meaning already indicated.

According to a third process, the product of formula IC is reacted with either a haloalkanoyl containing from 2 to 5 so carbon atoms, or a haloacid of formula Hai-CO-COOR ', in which R7 has the meaning already indicated, to obtain a product of formula:

55

60

(II)

(ID)

“S in which X represents an alkanoylamino radical containing from 2 to 5 carbon atoms or a group of formula —NH-CO-COOR ', in which R' has the meaning already indicated.

623,053

6

According to a fourth method, the product of formula IB is reduced to obtain the corresponding amino derivative of formula IC and the latter is hydrolyzed to obtain a product of formula:

H2

(IF)

If desired, the products of formulas IB, IC, ID and IF can then be salified.

Under preferred conditions for implementing the invention, the preparation methods described above are carried out as follows:

a) the decarboxylation of the product of formula II is carried out by heating the product,

b) the nitration of the product of formula IA is carried out by means of a mixture of concentrated nitric and sulfuric acids,

OOR.

(IB)

The product of formula IE is then reacted with a product of formula

R "—OH

(VI)

in which R "has the meaning of R, with the exception of a hydrogen atom, to obtain a product of formula:

he

° 2

20

(IJ)

in which R "has the meaning already indicated.

The product of formula IE or a functional derivative thereof is also reacted with a product of formula:

30

c) the reduction of the product of formula IB is carried out by means of a mild reducing agent such as stannous chloride and preferably in an acid medium.

d) the reaction of the product of formula IC with haloalka-nucleus or with the haloacid of formula Hai-CO-COOR 'is carried out in the presence of an organic solvent such as dimethylformamide.

In the process described above, the haloalkanoyl can advantageously be an alkanoyl chloride such as acetyl chloride. Likewise, the haloacid of formula: Hal-CO — COOR ′ can advantageously be the acid chloride of formula: Q — CO — COO — R 'in which R' has the meaning already indicated.

The subject of the invention is also methods of preparing the products defined by formula I above in which X represents a nitro radical and Z has the meaning already indicated, as well as their salts. To this end, a product of formula is first prepared, according to the first process indicated above.

Ri

HO- (CH2) n-N

/ \

(IV)

R2

to obtain a product of formula:

/ R1

fC00- (CH) -NC

2 n R „

(IG)

45 or with a product of formula:

Ri

H-N

50

(V)

R2

to obtain a product of formula:

in which R3 represents an alkyl radical containing from 1 to 5 carbon atoms, then hydrolyzes said product to obtain a product of formula:

JOOH

, R,

"0 0

(IE)

"Or,

(IH)

In the formulas above, n, Ri and R2 have the meanings already indicated, it being understood that when the products of

7

623,053

mule IV or of formula V contain a group> NH, this group must be protected during the reaction with the acid of formula IE or its functional derivative, then eliminates, where appropriate, the protective groups in order to obtain the sought after formula I products and, if desired, salify the latter.

Under preferred conditions for implementing the invention, the preparation methods described above are carried out as follows:

10

a) the hydrolysis of the products of formula IB and IC is carried out by means of an aqueous solution of an alkaline base such as sodium hydroxide,

b) the reaction of the compound of formula IE with the compound of formula IV or V is carried out in the presence of an organic solvent that is anhydrous,

c) the functional derivative of the product of formula IE is acid chloride and can be obtained by reaction of said product with a halogenating agent chosen from the group consisting

with thionyl chloride and a phosphorus halide. 20

In the processes defined last, the term protected amino radical designates for X either an alkanoyla-mino group as defined above, or a group —NH— CO — COOR 'in which R' represents a 2s alkyl radical containing 1 to 5 carbon atoms.

The functional derivative of the product of formula IR may for example be a product of formula:

(IX)

in which R3 has the meaning already indicated, followed by hydrogenation of the latter to obtain a product of formula:

COOR

3 (VIII)

° 2

30

(III) "

in which R3 has the meaning already indicated, then reaction of the latter with the halogenated derivative of a haloacetyl of formula Hai — CO — CH2 — Hai, in which Hai represents a chlorine, bromine or iodine atom, to obtain a product of formula:

^ C0CH2Hal NH H

40

COOR.

(VII)

in which Hai represents a halogen atom such as the chlorine, bromine or iodine atom.

The reaction of the product of formula IH with a product of formula IV or V is preferably carried out in an anhydrous organic solvent such as dichloromethane. The phosphorus halide used to prepare the products of formula III can be trichloride, phosphorus tribromide or phosphorus pentachloride. The salts of the products of formula I can be prepared by reacting said products with the corresponding acids or bases in substantially equimolecular proportions.

The starting product of formula II can be obtained by reaction of a product of formula:

COOR.

(X)

in which R3 has the meaning already indicated, with an organic nitrite to obtain a product of formula:

in which R3 and Hai have the definition already indicated; finally, the product of formula VII thus obtained is treated with a base and then with an acid to give the compound of formula II.

In the implementation of the process defined above:

a) the organic nitrite can advantageously consist of amyl nitrite,

B) the halogenated derivative of a haloacetyl of formula: Hai — CO — CH2 — Hai is advantageously chloroacetyl chloride,

c) the reaction of the product of formula VII with a base is advantageously carried out by means of a weak base such as sodium carbonate and followed by the treatment of a strong acid such as concentrated hydrochloric acid.

The products obtained by the processes which are the subject of the present invention have very advantageous pharma-60 ecological properties, they are endowed in particular with remarkable antiallergic and bronchodilator properties.

These properties justify the use of the derivatives of formula I and their pharmaceutically acceptable salts as medicaments.

65 Among these derivatives of formula I and their pharmaceutically acceptable salts, there are in particular those described in the examples. As medicaments, the derivatives of formula I and their pharmaceutically acceptable salts, are found by

623,053

8

for example, their use in the treatment of allergic asthma and asthmatic bronchitis of allergic origins.

The usual dose, which varies depending on the product used, the subject treated and the condition in question, may for example be 0.5 mg to 100 mg per day orally in humans.

The products of formula I, as well as their pharmaceutically acceptable salts, can be used to prepare pharmaceutical compositions, containing, as active principle, at least one of said products or at least one of said salts.

As medicaments, the derivatives corresponding to formula I and their pharmaceutically acceptable salts can be incorporated into pharmaceutical compositions intended for the digestive or parenteral or local route.

These pharmaceutical compositions can be, for example, solid or liquid and can be in the pharmaceutical forms commonly used in human medicine, such as, for example, tablets, simple or coated, capsules, granules, syrups, aerosols, suppositories , injections, ointments, creams; they are prepared according to the usual methods. The active ingredient (s) can be incorporated therein into excipients usually used in these pharmaceutical compositions, such as talc, gum arabic, lactose, starch, magnesium stearate, cocoa butter, aqueous vehicles or not , fatty substances of animal or vegetable origin, paraffinic derivatives, glycols, various wetting agents, dispersants or emulsifiers, preservatives.

The process of the invention makes it possible to obtain, as a new industrial product, useful in particular for the preparation of the derivatives corresponding to formula I, the product of formula II:

, COOCH.

I00H

The following examples illustrate the invention.

Preparation of the starting product Stage A: a-oximino-2-oxo-2H-1,4-benzoxazine-3-methyl acetate 82 g of 2-oxo-2H-1,4-benzoxazine-A3 are suspended ( 4H) methyl α-acetate (described in Bull. Chem. Soc. Japan 1971,44 (5), pages 1311 to 1313) in a liter of glacial acetic acid, 15 g of trichloroacetic acid are added followed by 48 g of amyl nitrite.

The temperature rises to around 60 ° C and the starting material goes completely into solution. After two hours, thin layer chromatography indicates that only a small amount of starting material remains. 3 g of amyl nitrite are added and the mixture is cooled for two hours in an ice bath.

The crystals obtained are filtered and washed with ether. After drying in the presence of P2O5, 74.4 g of expected product are obtained.

The mother liquors are concentrated at 70 ° C. to a volume of approximately 200 cm3 and a second jet of 2.3 g of product is obtained, ie in total 76.7 g of the expected product. Mp 169-170 ° C.

Spectrum I. R. (KBr)

Absorption at 771, 979, 1022, 1250, 1288, 1754, 3310 cm "1.

Stage B: a-amino-2-oxo-2H-1,4-benzoxazine A3 (4H) a-methyl acetate.

42.5 g of a-oximino-2-oxo-2H-1,4-benzoxazine-3-methyl acetate obtained in Stage A are suspended in 500 cm3 of dry tetrahydrofuran and 0.7 g of oxide are added of platinum. The mixture obtained is hydrogenated under a pressure of 4 atmospheres. The hydrogenation is rapid and regular and is completed after an hour and a half.

The dark red solution obtained is filtered on celite and the filter is washed with chloroform. The filtrate is evaporated to dryness at 45 ° C.

The residue is triturated in 100 cm 3 of cold ethanol. The red crystallized product thus obtained is filtered, washed with ethanol and ether and then dried. 35.5 g of expected product are obtained. M = 122-125 ° C.

Spectrum I. R. (KBr)

Absorption at 750,1218,1241,1280,1302,1510,1556, 1695,1728, 3300, 3360 and 3470 cm-1.

Stage C: 2-chloroacetamido-2- (2-oxo 2H-1,4-benzoxazin-3-yl) methyl acetate.

50.2 g of product obtained in Stage B are suspended in 400 cm3 of glacial acetic acid and 30 g of monochloroacetyl chloride are added. A yellow precipitate forms which dissolves when hot. After three hours at 50 ° C, thin layer chromatography indicates that the starting material has disappeared. The acetic acid is evaporated, 150 cm 3 of ethanol are added to the residue, the mixture is triturated and cooled. The crystals are filtered and washed with ether and, after drying, 52.6 g of yellow crystals are obtained.

Mp 129-131 ° C.

Spectrum I. R. (KBr)

Absorption at 765,1226,1533,1670,1745,1767, 3295 cm "1.

Stage D: 4H-2-methoxycarbonyl imidazo- [2, 1-c] [1, 4] benzoxazine-1-carboxylic acid.

72 g of the product obtained in Stage C are suspended in a mixture of 400 cm3 of water and 50 cm3 of acetone. 40 g of anhydrous sodium carbonate are added to the solution thus obtained, the mixture obtained is heated in a water bath for fifteen minutes until a clear yellow solution is obtained. Concentrated hydrochloric acid is added slowly with stirring to the hot solution until pH 2-3. A solid product crystallizes immediately and after cooling in an ice bath, is filtered. Washed with water, dried in the presence of P2O5 and obtained 43.5 g of the expected product; Mp 160-162 ° C.

Spectrum L R. (KBr)

Absorption at 750,1243,1276,1508,1554,1722 cm-1.

Example 1 Stage A: 4H-imidazo- [2, 1-c] [1, 4] -benzoxazine methyl 2-carboxylate.

Heated with stirring at 175-180 ° C for about twenty minutes, 20 g of product obtained in stage D. The decarboxylated product thus obtained is dissolved in chloroform, the solution obtained is passed over silica in order to remove the impurities. The solution of methyl 4H-imidazo- [2, 1-c] [1,4] -benzoxa-zine-2-carboxylate is brought to dryness, triturated in ether, filtered, washed with ether and dried. 14 g of expected product are obtained. Mp 133-134 ° C.

Spectrum I. R. (KBr)

Absorption at 745, 1259.1562, 1715.3135 cm-1.

Stage B: 8-nitro 4H-imidazo [2, lc] [1,4] -benzoxazine-2-methyl carboxylate 8 g of product obtained in stage A are introduced into a mixture of 25 cm3 of concentrated sulfuric acid and 25 cm3

s

10

15

20

25

30

35

40

45

50

55

60

65

concentrated nitric acid with stirring at 10 ° C. The starting ester gradually goes into solution, the solution turning yellow, and after three hours at room temperature, thin layer chromatography indicates that the starting product has disappeared. 500 cm3 of water are added, the yellow crystallized product obtained is filtered, washed with water, dried in the presence of P2O5 and finally 7.5 g of expected product is obtained.

Mp 270-272 ° C.

Spectrum I. R. (KBr)

Absorption at 1276,1348,1541, 1728, 3150 cm-1.

Example 2 Methyl 8-amino 4H-imidazo [2, 1-c] [1, 4] -benzoxazine 2-carboxylate.

5 g of product obtained in Example 1 are suspended in a mixture of 20 cm3 of acetic acid and 15 cm3 of concentrated hydrochloric acid. 15 g of stannous chloride are added to the solution thus obtained. The mixture obtained is stirred at 40 ° C. and after one hour a crystallized product appears. The mixture is cooled for two hours in an ice bath, filtered and the filter washed with ether. The product is dissolved in water, brought to pH 9 by addition of a sodium hydroxide solution. The product is extracted with chloroform, the organic phase is dried, and evaporated to dryness. The residue is triturated in ether and 2.7 g of brown crystals are obtained.

Mp 213-214 ° C.

Spectrum I. R. (KBr)

Absorption at 1740, 3135.3215, 3320.3440 cm-1.

Example 3 Methyl 8-acetamido 4H-imidazo [2, 1-c] [1, 4] -benzoxazine-2-carboxylate.

The operation is carried out as described in stage C of the preparation of the starting product, starting from the product prepared in Example 2 and acetyl chloride in dimethylformamide. The expected product is obtained.

Mp 216-219 ° C. Yield: 72 ° C.

Spectrum I. R. (KBr)

Absorption at 1510,1700,1750, 3040 cm-1.

Example 4

8- (ethoxalylamino) 4H-imidazo- [2, lc] [1,4] -benzoxazine-2-methyl carboxylate The procedure is carried out as described in stage C of the preparation of the starting product, starting from the product prepared for Example 2 and ethyl chloro Oxalate in dimethylformamide. The expected product is obtained.

Mp 186-188 ° C. Yield: 65%.

Spectrum I. R. (KBr)

Absorption at 1560, 1712, 1739, 3150.3300 cm-1.

Example 5 8-nitro 4H-imidazo- [2, l-c] [1,4] -benzoxazine-2-carboxylic acid 10 g of product obtained in Example 1 are suspended

623,053

in a mixture of 100 cm3 of methanol and 50 cm3 of water. A 2N sodium hydroxide solution is added up to pH 11, the mixture is heated until the starting material is completely dissolved. Thin layer chromatography indicates that the starting material has disappeared. The solution obtained is acidified to pH 2-3 by addition of concentrated hydrochloric acid, the expected product precipitates and after having cooled, it is filtered and washed with water. The product obtained is dried in the presence of P2O5 and the expected product is finally obtained.

Mp 310-312 ° C. Yield: 83%.

Spectrum I. R. (KBr)

Absorption at 1270,1352,1539, 1571,1690 cm-i.

EXAMPLE 6 Tris (hydroxymethyl) amino methane salt of 8-nitro 4H-imidazo acid [2,1-c] [1,4] -benzoxazine-2-carboxylic 6 g of product obtained is suspended Example 5 in methanol and add 3.5 g of tris (hydroxymethyl) amino methane. By heating, a clear solution is obtained. Cooled, initiates crystallization and finally obtains, after filtration and drying, the expected product in the form of crystals.

Example 7

4H-N- (N'-methyl-piperazinyl) 8-nitro imidazo-

[2,1-c] [1,4] -benzoxazine-2-carboxamide Stage A: 8-nitro acid chloride 4H-imidazo [2, lc] [1,4] -benzoxazine-2-carboxylic acid in suspension 5 g of the product obtained in Example 5 in 15 cm3 of thionyl chloride and brought to reflux for two hours, the excess of thionyl chloride is removed under reduced pressure by entraining it with benzene. The residue is triturated in ether, filtered and dried, the expected product is obtained.

Stage B: 4H-N- (N'-methyl-piperazinyl) 8-nitro imidazo [2, lc] [1,4] -benzoxazine-2-carboxamide 1 g of the acid chloride obtained in stage A is suspended in dry dichloromethane and add 1 g of N-methyl-piperazine. After three hours of stirring at room temperature, thin layer chromatography indicates that the starting material has disappeared. The solution is washed with water, dried and evaporated to dryness, the residue is triturated in ether and the expected product is obtained.

Example 8

8-nitro 4H-imidazo [2,1-c] [1,4] -benzoxazine-2-2-morpholinoethyl carboxylate 1 g of the acid chloride obtained in Stage A of Example 7 is suspended dry dichloromethane and add 1.31 g of N- (2-hydroxyethyl) -morpholine. The mixture obtained is heated at 50 ° C for two hours. Thin layer chromatography indicates that the starting material has practically disappeared. The mixture is washed with water, dried and evaporated to dryness. The residue is chromatographed on silica, eluting with ethyl acetate. The expected product is finally obtained.

9

5

10

is

20

25

30

35

40

45

50

55

B

Claims (17)

623,053 2 CLAIMS 1. Process for the preparation of new imidazobenzoxazines and their salts, said imidazobenzoxazines corresponding to the formula: OOR. 10 (IB) OOR. (II) in which R3 has the meaning already indicated, to obtain a compound of formula: OOR. in which R3 represents an alkyl radical containing from 1 to 5 carbon atoms, characterized in that a compound of formula IB above is prepared, by the process according to claim 1, and said compound is reduced. 4. Method according to claim 3, characterized in that compounds of formula IC are prepared in which R3 represents a methyl or ethyl radical, as well as their salts. 5. Process for the preparation of a new imidazobenzoxa-zine and its salts, said imidazobenzoxazine corresponding to the formula: 15 in which R3 represents an alkyl radical containing from 1 to 5 carbon atoms, characterized in that a compound of formula: 20 is decarboxylated (IE) 25 characterized in that, by the process according to claim 1, a compound of formula IB above is prepared and said compound is hydrolyzed. 6. Process for the preparation of new imidazobenzoxazines and their salts, said imidazobenzoxazines corresponding to the formula: OOR. 35 (ID) and nitrate said compound. 2. Method according to claim 1, characterized in that compounds of formula IB are prepared in which R3 represents a methyl or ethyl radical, as well as their salts. 3. Process for the preparation of new imidazobenzoxazines and their salts, said imidazobenzoxazines corresponding to the formula: COOR3 (XA) 45 in which R3 represents an alkyl radical containing from 1 to 5 carbon atoms and X represents an alkanoyla-mino radical containing from 2 to 5 carbon atoms or a group of formula - NH — CO — COOR ', in which R represents a hydrogen atom or an alkyl radical containing 50 of 1 to 5 carbon atoms, characterized in that a compound of formula EB is prepared by the process according to claim 1, said compound is reduced to obtain a compound of formula IC above and the compound is reacted with a haloalkanoyl containing 2 to 5 carbon atoms or with a halo acid of formula: Hal-CO-COOR ' in which R 'has the meaning already indicated. 7. Method according to claim 6, characterized in that compounds of formula ID are prepared in which X represents (IC) has an acetamido radical or a group of formula —NH-CÖ-COOR ', in which R' represents a hydrogen atom or a methyl or ethyl radical, and R3 represents a methyl or ethyl radical, as well as their salts. 8. Process for the preparation of a new imidazobenzoxazine and its salts, said imidazobenzoxazine corresponding to the formula: 55 60 3 623,053 OOH (IP) characterized in that, by the process according to claim 1, a compound of formula IB above is prepared, said compound is reduced to obtain a compound of formula IC above and this compound is hydrolyzed. 9. Process for the preparation of new imidazobenzoxazines and their salts, said imidazobenzoxazines corresponding to the formula: -R, ° 2 P00- (CH2) n-M in which n is equal to 1.2 or 3, Ri and R2, identical or different, represent a hydrogen atom or an alkyl radical containing from 1 to 5 carbon atoms, or Ri and R2 form together with the atom of nitrogen to which they are linked, a saturated heterocycle containing from 4 to 6 carbon atoms and which may, if desired, contain another heteroatom which may, if necessary, be substituted by an alkyl radical containing 30 from 1 to 5 atoms of carbon, characterized in that, by the process according to claim 1, a compound of formula IB above is prepared, said compound is hydrolyzed to obtain a compound of formula IE above and this compound or a derivative is reacted functional thereof with an amino alcohol of formula: HO- (CH2) n-N / ' \ (IV) R2 in which n, Ri and R2 have the meanings already indicated. 10. Method according to claim 9, characterized in that compounds of formula IG are prepared in which Ri and R2 form, together with the nitrogen atom to which they are linked, a pyrrolidino, piperidino, morpholino or 4 radical. -methyl pipé-razin-l-yl, as well as their salts. 11. Method according to claim 9, characterized in that so a compound of formula IG is prepared in which n is equal to 2 and - NR1R2 represents a morpholino radical. 12. Process for the preparation of new imidazobenzoxazines and their salts, said imidazobenzoxazines corresponding to the formula: ss (IG) in which Ri and R2, identical or different, represent a hydrogen atom or an alkyl radical containing from 1 to 5 carbon atoms, or Ri and R2 form together with the nitrogen atom to which they are linked, a saturated heterocycle containing from 4 to 6 carbon atoms and which can, if desired, contain another heteroatom which can, if necessary, be substituted by an alkyl radical containing from 1 to 5 carbon atoms, characterized in that one prepares, by the process according to claim 1, a compound of formula IB above, said compound is hydrolyzed to obtain a compound of formula IE above and this compound or a functional derivative thereof is reacted with an amino compound of formula: Ri HN ^ 40 \ (V) Rz in which Ri and R2 have the meanings already indicated. 13. Method according to claim 12, characterized in that compounds of formula IH are prepared in which Ri and R2 form, together with the nitrogen atom to which they are linked, a pyrrolidino, piperidino, morpholino or 4- radical. methyl piperazin-1-yl, and their salts. 14. Method according to claim 12, characterized in that a compound of formula IH is prepared in which -NR1R2 represents a 4-methyl piperazin-1-yl radical, as well as its salts. 15. Process for the preparation of new imidazobenzoxazines and their salts, said imidazobenzoxazines corresponding to the formula: ° 2 / R1 R, (IH) COOR " (IJ) 623,053 4 in which R "represents an alkyl radical containing from 1 to 5 carbon atoms or a group of formula: Ri - (CH2) n-N ' in which n is equal to 1,2 or 3, Ri and R2, identical or different, represent a hydrogen atom or an alkyl radical containing from 1 to 5 carbon atoms, or Ri and R2 form together with the atom d nitrogen to which they are linked, a saturated heterocycle containing from 4 to 6 carbon atoms and 1 s which may, if desired, contain another heteroatom which may, if appropriate, be substituted by an alkyl radical containing from 1 to 5 atoms carbon, characterized in that, by the process according to claim 1, a compound of formula IB above is prepared, said compound is hydrolyzed to obtain a compound of formula IE above and this compound is reacted with a formula alcohol: R "OH (VI) in which R "has the meaning already indicated. 16. Method according to claim 15, characterized in that compounds of formula U are prepared in which R "represents a methyl or ethyl radical or a group of formula - (CH2) n-N ' in which Ri and R2 form, together with the nitrogen atom to which they are linked, a pyrrolidino, piperidino, morpho lino, piperazino or 4-methyl piperazin-1-yl radical, as well as their salts. 17. The method of claim 15, characterized in that compounds of formula U are prepared in which R "represents a methyl, ethyl or morpholino ethyl radical, as well as their salts. 1- 40 45 Certain heterocyclic compounds with a structure close to that of the compounds of formula I described below were already known (US Pat. No. 3,929,783).