SU1082324A3 - Process for preparing condensed derivatives of pyrimidine or their salts - Google Patents

Abstract

Compounds of the general formula <IMAGE> [wherein R and R<1> are H or C1-4alkyl, or together form (CH=CH)-2, R<2> is H or C1-4alkyl R<3> is H, C1-4alkyl, phenyl, carboxy or salt thereof, alkoxycarbonyl, carbamoyl, cyano, -CO-NH-CO-SO2-C6H4-p-CH3 or -(CH2)s-COOR<14> (s is 1, 2 or 3 and R<14> is H or C1-4alkyl, n is 0 or 1, (a) if R<13> is H, and R<12->R<11> and R<9->R<10> form bonds then YR<7>R<8> represents oxygen or sulfur, or Y represents nitrogen, R<7> is C1-4alkyl, optionally substituted C6-10aryl or C7-12aralkyl, R<8> is a lone pair of electrons or C1-4 alkyl and in this latter case a salt is formed; and XR<4>R<5>R<6> represents halogen; or XR<5>R<6> represents oxygen or sulfur, and R<4> is H or C1-4alkyl, XR<6> represents nitrogen and R<4> is chloroacetyl, C1-4alkyl or optionally substituted C6-10aryl or heteroaryl and R<5> is H or alkyl or (b) if R<11> is H and R<9->R<10> and R<12->R<13> form bonds, then R<4>, R<5>, R<6>, R<7>, R<8>, X and Y are as defined in item (a) and (c) if R<10->R<11> and R<12->R<13> form bonds, then YR<7>R<8>R<9> represents an oxygen or sulfur anion or YR<8>R<9> represents oxygen or sulphur and R<7> is H or C1-4alkyl; or YR<9> represents nitrogen, R<7> is H, C1-4alkyl or optionally substituted C6-10aryl, and R<8> is C1-4alkyl, and XR<4>R<5>R<6> represents halogen or an oxygen or sulfur anion or XR<5>R<6> is O or S and R<4> is H or C1-4alkyl, or XR<6> represents nitrogen, R<4> is chloroacetyl, C1-4alkyl or optionally substituted C6-10aryl or heteroaryl and R<5> is H or C1-4alkyl, and if YR<8>R<9> and XR<5>R<6> each represent oxygen or or sulfur or if YR<9> and XR<6> each represent nitrogen (R<5> and R<8> each being H or C1-4alkyl), then R<4> and R<7> together form optionally substituted -(CH2)-s (s is 1, 2, 3 or 4)] and the tautomers and salts thereof. The compounds have physiological activity.

Description

nor a compound of general formula I, where. have the indicated meanings, and Rg, Rj fc form together. bond, and Rg — C;, —C — alkyl, or a compound of the general formula I, where Rj is alkoxycarbonyl, the hydrolysis residue and the desired product are isolated as a base or salt.

The invention relates to a process for the irradiation of new condensed pyrimidine derivatives, which can be used as intermediates in the synthesis of drugs. The reaction of C-acylation of 1,2-dihydropyridine derivatives in the presence of a base in a solvent or in the absence of a solvent at a temperature flj is known. The purpose of the invention is to obtain new condensed pyrimidine derivatives, which can be used as intermediate products in the synthesis of medicinal substances. The goal is achieved by the method of obtaining condensed pyrimidine derivatives of the general formula where p is or 1; R-I and Yal - hydrogen or.-Alkyl; R3 is carboxyl or its alkali salt, -alkoxycarbonyl, carbamoyl, or the group CONHCONHS02C; Y is oxygen or sulfur; R4. C. d-alkyl, chloroacetyl; n is methylbenzenesulfonyl, unsubstituted phenyl or phenyl, substituted by.-alkyl, hapogen, trifluoromethyl,.-alkoxy, etc. provided that if Rj - and R as well as R and Rj form together a bond, then Rg is hydrogen, - or, if Rj and Ri, and also Ц and сп form together сп and Y is sulfur, then R with | - C., - Cd alkyl or their co. Pep wherein the compound of the general formula B, -f I Xxlv R, where the R-RT type have the indicated meanings, is acylated with the compound of the general formula Ri, where R and p have the indicated values, in the presence of a base and, if necessary, in an inert solvent, such as chlorinated aromatic or aliphatic hydrocarbons at 20-100 ° C, followed by isolation of the target product, or the resulting compound of general formula (I), where they have the indicated values, and Y is sulfur, R . and Rg, as well as R and RJ form a bond in RST and Rg are hydrogen, are alkylated in the presence of acid acceptors for the preparation of compounds of the general formula (I), where they have the indicated meanings, and R-, and Rg, Rj. and R forms a bond together, and RQ. -alkyl, or a compound of the general formula (I), where RJ is alkoxycarbonyl, is hydrolyzed and the desired product is isolated as a base or salt. 1-3 mol of the compound of the general formula (III) are used for each mole of the compound of the general formula (II). Alkyl halides, such as methyl iodide, ethyl bromide, dialkyl sulfates, such as methyl sulfate, diethyl sulfate, trialkyl phosphates such as triethyl phosphate, trialkyloxonium fluoroborates, can be used to acidify a compound of general formula (I). The alkylation is preferably carried out in a solvent at 0-160 ° C. Examples 1-4. To a solution of 0.05 mol of pyrido 1 .2-c-) pyrimidine in dichloromethane, in kashigm, mol / isocyanate is added at room temperature. The reaction mixture is boiled for 10 hours and left to stand for 2 days at a phenyliso-3-ethoxycar-46 200-201 cyanate bonyl-6-me3-ethoxycarbonyl-6-chloroace-methyl-4-oxo-6, 7 , 8J tiliso9-tetrahydro-4H-cyanate rido D, 2-a pyrimidine

Tozilizo-3-Etoksikar- 80 182-183

cyanate

3-Amino Arbonyl-6-metsh1-4-oxo-6, 7,8 | 9 -tetrahydro-4H-pyrido Cl, 2-a pyrimidine

then the solvent is distilled off. The resulting compounds are listed in tsgbl, 1.

Table. one

Tyl-9- (K-phenylaminocarbonsh1) -4-oxo-6, 7,8,9- ... tetrahydro-4H-pyrido 1,2-a pyrmicin

158-160

74

9

Bonil-6-methyl-9-TOZYL-aminocarboNYL-4-OXO-6, 7,8,9-tet

rahydro-4NpirioS, 2-aJ

pyrimidine

3-Tosylamino

carbonyl-b-methyl-9-tosylaminocarbonyl-4-oxo

6,758,9-tetrahydro-4Npirido tl, 2-a

pyrimidine

2

So

H and 1 mole of the original substance

Examples 5-9. A mixture of 23.6 g of 3-ethoxycarbonyl-6-methyl-4-oxo-4H-pyridoC, 2-a pyrimidine and 0.1 mol of JQ isocyanate, stirring for 72 hours at 40-50 C. The resulting viscous reaction mixture is suspended at

Continued table. one

64.21 / 63.95 5.95 / 5.81 11.83 / 11.65

50.63 / 51.02 5.06 / 5.02 11.80 / 11.69

55.42 / 55.92 5.35 / 5.30 9.69 / 2.72

51.90 / 52.28 4.52 / 4.48 11.64 / 11.51

2.1 moles of isocyanate are used.

200 ml of ethanol, filtered and flushed

ethanol. (In case, if H-butyl isocyanate is used, the reaction is carried out at 80-100 ° C).

The resulting compounds 1 are presented in Table 2.

Z-Ethoxycarbonyl-6-methyln-Butyliso-, -9- (H-butylaminecarbonyl) cyanate-4-OXO-6,7,8,9-tetrahydro-4H-pyrido f 1,2-a pyrimidine

b Phenyl isocyanate 3-Ethoxycarbonyl-6-: methyl- 74 198-200 -9-phenylaminocarbonyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido f 1,2-a pyrimidine

3-Ethoxycarbonyl-6-methyl- 82 206-10

4-Chlorophenyl- - (4-chlorophenylaminocarboisocyanate Nile) -4-ОКСО-6, 9-tetrahydro-4H-pyrido 1, 2-a1-pyrimidine

3-Ethoxycarbonyl-6-methyl- 78 194-198

3-Chlorophenyl-9- (3-chlorophenylaminocarisocyanate bonyl) -4-OXO-6,7,8,9-tetrahydro-4H-pyrido l, 2-c (pyrimidine

3-Ethoxycarbonyl-6-methyl3, 4-Dichlorf-9- (3,4-dichlorophenylamide or isocarboyl) -4-oxo-1,6,7,8-tetrahydro-4H-pyrndo 11-, 2- and pyrimidine

one

S7V3

6

CieV3 ° 4 i

C.-1TNO C1 58.50 / 58.21 5.13 / 5.05 10.78 / 10.61 20 oe 4

 , 58.80 / 53.28 4.48 / 4.40 9.90 / 9.78

table 2

35 152-155

79 208-212

Continued table. 2

60.90 / 60.25 7.47 / 7.41 12.52 / 12.40

No decrease in m. with the product of example 20

58.50 / 58.10 5.13 / 5.07 10.73 / 10.59 Example 10. A mixture of 2.0 g of 3-amnocarboni "g1--2.6-: dimethyl-4-oxo-6, 7.8 9 tetrahydro-4H-pyrido 1 2-a} pyrimidine and 2.2 g of phenyl isoacetate are heated to 80 ° C and the resulting solution is re-converted at 50-60 ° C. After cooling, the reaction mixture is treated with 30 ml of ether, precipitated crystals is dissolved in ethanol, filtered, and the filtrate is subjected to crystallization in a cold store, the precipitated crystals are filtered and washed with ethanol. 1.4 g of 3-aminocarbonyl-9-phenyl aminocarbonyl-2,6-dimethyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido 1, 2-a pyrimidine is obtained, which melts at 187- 188 C. Found,%: C 63.49; H 6.00 ;, N 16.26. CiaH2o 4Q3 Calculated; %: C 63., 5; H 5.92; N 16.46. Example 11. Dissolve 1.6 g of potassium hydrochloride in 20 g of "w ethanol. To the ethanolic solution of potassium hydrochloride add an ethanol solution of 3.6 g of C-ethoxycarbonyl-9-phenylaminocarbonyl-6 - methyl-4 oxo-6, 7,8,9-tet rahidro-4H pyrido, 2-a pyrimidine. The reaction mixture is boiled for 30 hours and the precipitate after cooling; -i, crista, filtered off, washed with Chloroform 5 is dried. 3.1 g of 9 phenylaminocarbonyl-6-methyl-4-oxo-b.7,8,9-tetrahydro-4H-pyrid t1; 2 and potassium ghrimidine-3-carboxylate are obtained, which melt with decomposition at 276-280 ° C. Found,%: C 56.02; H 4.50; N 1.42, C ,,,. To Vmisleno,%: C 55.88; H 4.41; N.11.50 Example 12. 3.1 g of 9-phenylaminocarbonyl-b-methyl-4-oxo-6, 7,8.9 potassium tetrahydro-4H-pyrido 1, 2-potassium gdarimidine-3-carboxylate are dissolved in 250 ml of water when heated, adjusted to pH 1 by the addition of 38 wt.% hydrochloric acid solution. Crystals entrained upon cooling are filtered, washed with water, dried. 2.2 g of crystals are obtained which are crystallized from acetonitrile. 9-phenylaminocarbonyl-3-carboxy-6 methyl-4-oxo-6, 7 p859-tetrahydro-4H-pyrido 1, 2-a PYRIMI7-1IN are obtained in (- 25%. Found: C, 62.18; H, 5.18; N, 12.45; Nbsp;% V, C, 62.37; H, 5.24; N, 12.84. Example 13. 0.416 g of H is dissolved. ethoxycarbonyl-4-oxo-5, 6,7,8-tetrahydropyrrolo-1,2-a1-pyrimidine in 4 ml of benzene and 0.24 g of phenyl isoacetate is added to the solution. The reaction mixture is left to stand for 5 days, at room temperature, after This precipitated crystals are filtered and washed with benzenes. 0.50 g (76.5% of t is obtained) eorium) 3-ztoxycarbonyl-9- (M-phenylaminocarbonyl) -4-OXO-5,6,7,8-tetrahydropyrrol1, 2-a pyrimidine, which melts at 240-241 ° C. Pavdeno,%: C 62.51 ; H 5515; N 12.90. C, H, CsO Calculated,%: C 62.38; H 5.23; N 12.84, Example 14. O, 66 g of an oil suspension of sodium hydride is added in 50 The benzene MP, after which a solution of 4.72 g of 3-ethoxycarbonyl-8-methyl-4-oxo-6, 7 58.9-tetrahydro-4H-pyrido 1,2-aj pyrimdine in 15 ml of benzene is added dropwise. After 30 minutes of stirring, add at 25-35. C for 10 min. A solution of 2.96 g of methyl thioisocyanate in 10 ml of benzene. The reaction mixture is stirred for 2 hours and then after adding 80 ml of ether, sodium salt of 3-ethoxycarbon-1-w-6-methyl-9-methylaminothiocarbonyl-4-oxo-6, 7,8,9-tetrahydro-4H pyrido Cl, 2 is obtained -AZ Pyrimi, Dina 3 kind of oil. The solvent is decanted, the residue is triturated with ether and dried in a vacuum oven. 3-ethoxycarbonyl-6-methyl-9-methylaminothiocarbonyl 4 oxo-6, 7,8,9-tetrahydro-4H-pyrido 1, 2-α-pyrimidine is obtained in the form of sodium salt. Example 15. To the sodium salt of 3-ethoxycarbonyl-6-methyl-9-methylaminothiocarbonyl 4-oxo-6,7,8,9-tetrahydro-4H-pyrido C 1,2-a pyrimidine prepared in Example 14 was added 15 ml. acetone, then 130 ml of water and set with acetic acid pH 3-4. The crystallized crystals are filtered, washed with water, dried, and crystallized from ethanol to obtain 3.2 g (52%) of 3-ethoxycarbonyl-6-me Tyl-9-methylaminothiocarbonip-4-oxo-6,7,8,9-tetrahydro-4H-distilled 1, 2 - pyrimidine, so pl. 199-200 S.. Found; %: C 54.55; H 6.18; N 13.72. Calculated,%: C 54.35; H 6.19; N 13.58. Example 16 0.66 g of a 90% oily suspension of sodium hydride is added to 50 ml of benzene, then added dropwise to 15 ml of benzene 4.72 g of 3-ethoxycarbonyl-6-methyl-4-oxo-6 , 7,8,9-tetrahydro-4H-pyrido, L1,2-a pyrimidine. After stirring for 30 minutes, 5.4 g of phenyl thioisocyanate in 10 ml of benzene is added at 25-35 seconds for 10 minutes. The reaction mixture is stirred for 2 hours and after adding 80 ml of ether, the sodium salt of 3-ethoxycarbonyl-6-methyl-9-phenylaminothiocarbonyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido 1, 2 is liberated. -and pyrimidine in the form of oil. The solvent is decanted, triturated with ether and dried in vacuo. Sodium salt of 3-ethoxycarbonyl-6-methyl-9-phenylamino-thiocarbonyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido 1, 2-a pyrimidine is obtained, yield 6.1 g (76%). Example 17. To the sodium salt of 3-ethoxycarbonyl-6-methyl-9-phenylaminothiocarbonyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido 1, 2-a pyrimidine prepared in Example 16 were added 15 MP acetone and 130 ml of water and adjust the pH to 3-4 with acetic acid. The crystals that have been isolated are filtered, washed with water, dried and crystallized from acetonitrile. 3.2g (52%) of 3-ethoxycarbonyl-6-methyl-9-phenylaminothiocarbonyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido l, 2-a pyrimidine are obtained, m.p. 173-175 ° C. Found,%: C 61.75; H 5.57; N 11.40. Calculated,%: C, 61.44; H 5.70; N 11.31. Example 18 The procedure is also as described in examples 5-9, but 4-methoxyphenyl isocyanate is used as the isocyanate. 3-ethoxycarbonyl-9 fN- (4-methoxyphenyl) -aminocarbonyl2-6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido 1 7 2 -a pyrimidine are obtained, yield 52%, m.p. 183-184 ° C. Found,%: C 62.45; And 6.00; N 10.85. CjoK NjO Calculated,%: C 62.33; H 6.02; N 10.90. Example 19. They also act as described in examples 5-9, but 3-methoxycarbonyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido 1, 2-a pyrimidine and phenyl isocyanate are used as the starting material. Get 3-methoxycarbonyl-9- (phenylaminocarbonyl) -4-oxo-1, 6,7,8-tetrahydro-4H-pyrido.1, 2-aJ pyrimidine, yield 71%, so pl. 173-175С. Found,%: C 62.47; H 5.21; N 12.79. -17Np "s04,%: C, 62.38; H 5.25; N 12.84. Example 20. Act as in Examples 5-9, but Z-methoxycarbonyl-6-methyl-4-oxo-6, 7.8, 4,9-tetrahydro-4H-pyrido 1, -2-a pyrimidine is used as the starting compound. and phenyl isocyanate. Get 3-methoxycarboxy 1-9-phenylaminocarbonyl-6-methyl-4-OXO-6, 7,8,9-tetrahydro-4H-pyrido 1, 2-aZpyrimidine, yield 74%, so pl. 199-200С. Found; %: C, 63.21; H 5.70; N 12.32. C gHi9N304 Calculated,%: C, 63.33; H 5.61; N 12.31 Example 21. Act as in Examples 5-9, but 3-ethoxycarbonyl-7-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido 1, 2- is used as the starting material. and pyrimidine and phenyl isocyanate. Get 3-ethoxycarbonyl-9-phenylaminocarbonyl-7-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido 1,2-aj pyrimidine, yield 55%, so pl. 216217 ° C. Found,%: - C 64.34; H 5.88; N 11.90. ClsS A Calculated,%: C 64.21; H 5.95; N 11.83. Example 22. Operate as described in examples 11-12, but as starting material use 3-ethoxycarbonyl-9-N- (4-methoxyphenyl) -aminocarbonyl 3-6-methyl-4-oxo-6, 7,8,9- tetrahydro-4H-pyrido |, 2-a pyrimidine. Yield 44%, mp. 201202 ° C. C, 60.38; And 5.19; Found,% i N I1,85. , Calculated,%: C 60.5C; N N 11, 67 Example 23 10 mmol 3-etoc scicarbonyl-6-methyl-9-methylaminothiocarbonyl-4-oxo-B7758, 9-tetrahydropyrido 1, 2-a Zpirimidine, 10 mmol sodium acetate and 3 ml of methyl iodide bale t in ethanol for 30 minutes and concentrated under reduced pressure. 10 ml of water and 60 ml of diethyl ether are added to the residue. After stirring for 20 minutes, the ether phase is separated and, after drying with anhydrous sodium sulfate and filtering, the mixture is concentrated to opalescence and crystallized at. The filtered crystals are recrystallized from ether. 3-ethoxycarbonyl-6-methyl 9 (methylenethiomethylamino) methylene 1-4 -oco is obtained -6 5 7.8 9-tetrahydro-4H-pyrido 1,2-a pyrimidine, yield 65%, so pl. 168170 ° C. Found,%: С 56, Н 6 „О; N 12.78. 15- 20 of 19%; C 55.53 | H 6.2 N12.95, PRI me R 24, Worked as olisano in Example 23, but 3-etoc of Sicarbonyl-6-methyL-9 ethylaminothioconyl 4 - oxo 6,7,8 , 9-tetrahydro-4H -nrido 1 5 2 -a pyrimidine. Get 3-ethoxycarbonyl-6-methyl-9 (methylthioethylamino) methylene-4-oxo-6,7,8, -tetrahydro-4H-pyrido 1,2-a pyrimide. with a yield of 53%, so pl. 119 Found;%: C 57.40; H N 12 ,, 42. Calculated,%: C 57.12; H 6.89; N 12.49. 25. They work as op and mep 23, but 3-ethoxy: carbonyl-6-methyl-9-phenylaminothiocaron-4-oxo-b, 7,8,9-tetrahydro-4H is used as an example of the starting substance. pyrido 1, 2-and pyrimidine. Get 3-ethoxycarbonyl-6-methyl-9- (methylthiophenylamino) methyleneJ-4-oxo-6,7,8 -tetrahydrs1-4H-pyrido 1, 2-a pyrimide with a yield of 36%, so pl. 11 O-112C. Found,%: C 62.64; H 5.81; . N 1.01. Il27f 3 "Calculated,%: C 62.46; H 5.77; N 10.93. Example 26. It was operated as described in Example 11 and 12, but 3-ethoxycarbonyl-6-methyl-9-phenylaminothiocarbonyl-4-oxo-6, 7,8,9-tetrahydr-1-shro-4H-pyrido was used as the starting material. 1, 2-aJ pyrimidine. 9-phenylaminothiocarbonyl-3-carboxyl-6 methyl 4-oxo-6, 7,8,9-tetrahydro-4H-pyrido: 1, 2-a pyrimidine are obtained in a yield of 58%, m.p. A9-121s (decomp.), Found,%: C 59.03; H 5.03; N 12.31. C ,,, H ,,, Calculated,%: C 59.45; H 4.99; N 12.23. Example 27. It is operated as described in Example 14 and 15, but ethylisothiodianate is used as an isodianate. Get 3-ethoxycarbonyl 6-methyl-9-ethylaminothiocarbonyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido 1, 2-a pyrimidine with a yield of 32%, which is recrystallized from ethyl acetate, so pl. 179-18 s, Navdeno,%; From 55.60 | H 6.42 N 13.07, S;, 95. C, 5H2, Nj03S Viiisleno,%: C 55.71; H 6.54; N 12.99, S 9.91 I, Example 28. Proceed as in examples 5-9 ,. but optically active (-) - 3-ethoxycarbonyl-b-methyl-4-OXO-6, 7,8,9-tetrahydro-4H-pyrio D, 2-aJ pyrimidine -111 ° is used as the starting product, ( 2, methanol} and phenyl isodianate, Received; ayut (-) -3-ethoxycarbonyl-6-methyl-9-phenylaminocarbonyl-4-oxo-6; 7,8,9-tetrahydro-4H-pyrido 1,2-a and irimz din , yield 45%, mp. 174176 C (after recrystallization from ethanol), ci -62 chloro (J) orm / methanol: 1). Found,%: C 64.11; And 6.03; N. 11, 84. Ci9H2, N30 Calculated,%: C 64.21; H 5.95; N 11, 83. Example 29: Proceed as in Examples 5-9, but optically active (+) - 3-ethoxycar5onyl-6-methyl-4-OXO-6, 7,8,9-tetra ti-dyro 4H-pyrido 1 5 2-a pyrim11dina oi g 1 10 °, (c 2, methanol) and phenyl isopianate. By

Claims (1)

The method of obtaining condensed pyrimidine derivatives of the general formula I where η is 0 or 1; R <1 and R? - hydrogen or C ^ -C ^ -alkyl; R ₃ - carboxyl or its alkaline salt, C „~ C-alkoxy | 4 carbopyl, carbamoyl or group - C0NH-C0NHS0 ₉ C, H CH, Z O 4 s Y is oxygen or sulfur; R ₄ ^_ Sη-C ^ -alkyl, chloroacetyl; η is methylbenzenesulfonyl, unsubstituted phenyl or phenyl. substituted with C ^ -C ^ -alkyl, halogen, trifluoromethyl, Cη-C ^ -apoxoxy provided that if R ₅ and also R ^ and Ry form a bond together, then Rg is hydrogen or if R _s and R ₆ as well as R _? and Rg together form a bond and Y is sulfur, then Rg is C ₇ -C alkyl or their salts, characterized in that the compound of general form wherein R ₇ ~ R ₃ and η have the indicated meanings, are acylated with a compound of the general formula III where and Y have these values, in the presence of a base and, if necessary, ^ in an inert solvent, such as chlorinated, aromatic or aliphatic hydrocarbons at 20-100 ° C followed by isolation of the target product, or the obtained compound of general formula I, where they have the indicated values, a Y is sulfur, R _s and R ^, and also Rj form together zy and Rg are hydrogen, are alkylated in the presence of an acid acceptor for the preparation of SUN 10823.24 of a compound of general formula I, where R ^ -R ^ have the indicated meanings, and R) and Rj, Rj and R _fc form together. bond, and R ₉ is C ^ -C ^ -alkyl, or a compound of general formula I, where Rj is alkoxycarbonyl, hydrolyzed and the desired product is isolated in the form of a base or salt.