• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Dihydropyridines of the formula:- …<CHEM>… and their pharmaceutically acceptable acid addition salts… wherein Y is -(CH2)2-, -(CH2)3-, -CH2CH(CH3)- or -CH2C(CH3)2-;… R is aryl or heteroaryl;… R<1> and R<2> are each independently C1-C4 alkyl or 2-methoxyethyl; and… R<3> is hydrogen, C1-C4 alkyl, 2-(C1-C4 alkoxyl) ethyl, cyclopropylmethyl, benzyl, or -(CH2)mCOR<4> where m is 1, 2 or 3 and R<4> is hydroxy, C1-C4 alkoxy or - NR<R>5<6> where R<5> and R<6> are each independently hydrogen or C1-C4 alkyl, pharmaceutical compositions containing them, and processes for their production. …<??>The compounds are particularly useful in the treatment or prevention of a variety of cardiac conditions, e.g, angina pectoris.
    公开号:SU1238730A3
    申请号:SU833571949
    申请日:1983-03-04
    公开日:1986-06-15
    发明作者:Фразер Кемпбелл Симон；Эдвард Кросс Питер；Кендрик Стаббз Джон
    申请人:Пфайзер Корпорейшн (Фирма)；
    IPC主号:
    专利说明:

    3. The method according to claim 2, wherein the X-NR (benzyl) and benzylic group removal is carried out by hydrogenation.
    4. A method according to claim. Wherein X is the group NRj-COOCHj CCl, and the group (COOCH2 CC15) is removed by the action of zinc and formic or acetic acid.
    5. Method 1, characterized by the fact that the X-phthalimido and-phthaloyl group are removed by exposure to methylamine, hydrazine hydrate or potassium hydroxide, and then hydrochloric or sulfuric acid.
    The invention relates to a method for producing novel I, A-dihydropyridine derivatives having pharmacological activity and which can be used in the prevention and treatment of myocardial infarction and hypertension.
    The purpose of the invention is a method for the preparation of 1,4-dihydropyridine derivatives or their acid addition salts, which have an activity in the prophylaxis and treatment of myocardial infarction and hypertension.
    The following examples illustrate the synthesis of compounds and their pharmacological activity.
    Example I. Preparation of 4- (2-chlorophenyl) -2- (2-methylamino) ethoxymethyl-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine oxalate acid salt.
    The solution of oxalate salt (H-benzyl-N-methylamino) -ethoxymethyl-1- 4- (2-chlorophenyl) -3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (4.3 g) in methanol (220 ml) was added to a suspension of 10 wt.% Palladium on activated carbon (0.4 g) previously hydrogenated in methanol (50 ml). Stirring at a pressure of 3.5 kg / cm hydrogen (50 psig) at room temperature overnight leads to the complete removal of the benzyl group. After removal of the catalyst by filtration
    methanol was evaporated and the residue was crystallized from a small amount of methanol to obtain the indicated compound (2.4 g), mp. 21l c.
    with
    to
    (five
    0
    5 Q
    five
    Calculated,%: C 53.85; H 5.70; N 5.46.
    C2, Hj7ClN20yC n 04
    Found,%: C 53.99; H 5.76; N 5.60.
    The free base has so pl. 88-90 ° C (from ether).
    Examples 2-10 (see tab.1). The following compounds are prepared by the method described in Example 1. The compounds are prepared from the oxalate of the corresponding N-substituted dihydropyridine by hydrogenation in the presence of palladium. Hydrogenation of the K, H-dibenzyl starting material in Example 8 results in a monobenzyl product, which, in turn, is used as the starting product in Example 9.

    Example 11 Methyl-K- {2- 4- (2,3-dichlorophenyl) -3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyrid-2-Sh1 methoxy-methyl amino acetate.
    A solution of methyl bromoacetate (1.53 g) in acetonitrile (20 ml) is added dropwise over 30 minutes to a mixture of 2- (2-aminosulfate methyl 1-4- (2,3-dichlorophenyl) -3-ethoxycarbon-1-5 -methoxycarbonyl-6-methyl-1,4-dihydropyridine (5.01 g) and potassium carbonate (2.76 g) in acetonitrile (60 ml) with stirring under reflux. Then the mixture is heated under reflux with another 3 hours, filtered and evaporated. The residue is partitioned between ethyl acetate and water. The organic layer is washed with water, dried with sodium sulfate and evaporated. The residue is chromatographed on silica (foreign company and Merck, trade name Kieselgel 60H, 40 g). Dichloromethane with 0-3% methanol is used for elution from the adsorbent. The desired fractions are combined and evaporated, the indicated compound is obtained (2.10 g), mp 96 -98 ° C.
    Found,%: C 53.25; H 5.49; N 5.48.
    C HzgCl Nz T
    Calculated,%: C 53.60; H 5.48; N 5.44.
    Examples 12 and 13 (see table. The following compounds are prepared according to Example 11 using the corresponding raw materials.
    EXAMPLE 14 2 - ((2-Chlorophenyl) -3-ethoxycarbonyl-5-methoxy-carbonyl-6-methyl-1,4-dihydropyrid-2-yl methoxy-e-thylamino) acetamide.
    Ethyl H - (((2-chlorophenyl) -3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1, 4-dihydropyrid-2-yl methoxy ethyl) aminoacetate (2.50 g) is mixed with ethanol (40 ml) and 0.880 n. aqueous ammonia solution (30 ml) and stirred at room temperature for 4 days, then evaporated. The residue was partitioned between ethyl acetate and water. The organic layer was washed with water, dried over magnesium sulfate, and evaporated. The residue is chromatographed on silica (Merck, Kieselgel Bon, 30 g) and eluted from the adsorbent with dichloromethane in a mixture with 0-5% methanol. The appropriate fractions are combined and evaporated. The residue is triturated with ethyl acetate, the resulting solid is collected, washed with ethyl acetate and dried to give the title compound (1.23 g), mp. 126-129 С
    Found,%: C 56.78; H 6.06; . N 8.68.
    C2jH28ClN, 06
    Calculated,%: C 56.71; H 6.06; N 9.02.
    Example 15 (see table 3). The following compound according to the method described in example 14, using the corresponding dihydropyridine and methylamine,
    EXAMPLE 16 M - ((2-chlorophenyl) -3-ethoxycarbon-1-5-methoxy-carbonyl-b-methyl-J, 4-dihydro-11-amide-2-yl methoxy-1-S1) amino-acetic acid.
    five
    ten
    15
    .
    25

    five
    thirty
    0
    five
    A solution of methyl-N- (2- (4- (2-chlorophenyl) -3-ethoxcarbonyl-5-methoxycarbonyl-6-methyp-1, 4-dihydropyrid-2-yl | methoxyYethyl aminoacetate (2.40 g ) in dioxane (80 ml) is treated with I n, an aqueous solution of sodium hydroxide (10 Mrt), and the mixture is stirred at room temperature for 2 hours, then evaporated. The residue is purified by ion-exchange chromatography (Bio-Rad, AG 50W - X8 200-400 mesh, cationic form, 40 g) eluting from the adsorbent, first with dioxane, then with 2% pyridine solution in water. The appropriate fractions are combined and evaporated, to obtain the indicated compound in the form of a hemihydrate (g), t. Square 140-50 C (with decomposition).
    Found,%: C 55.52; H 5.95; N 5.92.
    27 27 207/2 HjO Calculated,%: C 55.52; H 5.93; N 5.89.
    ft pm. mep 17. Preparation of 2- (2-aminoethoxy) methyl -4- (2-chlorophenyl) -3-ethoxycarbonyl-5-metaxycar, bonyl-6-methyl-1,4-dihydropyridine maleate.
    Method A {using a solution of methylamine in ethanol).
    4- (2-Chlorophenyl) -3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-2- (2-phthalamidoethoxy) methyl-1,4-dihydropyridine (80 g) is stirred in a 33% solution methylamine in ethanol (1067 ml) at room temperature for 3 hours. Then the solvent is evaporated, the residue is suspended in decagurate (technical ethyl alcohol) (300 ml),. then filtered. Maleic acid (17.4 g) is added to the filtrate and, after stirring, a precipitate is obtained. It is collected by filtration and washed with denatured alcohol. A solid is crystallized from the indicated denatured alcohol (430 ml) and dried at 55 s to obtain the indicated compound (38.4 g) as a white solid. According to spectroscopic data, this substance is identical to the products obtained in examples 9 and 12.
    Method B (use of hydrazine hydrate).
    4- (2-Chlorophenyl) -3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl -2- (2-phthalimidoethoxy) methyl-1,4-dihydropyridine (383 g) is stirred in ethanol containing hydrazine hydrate ( 106.7 g), at boiling with reflux condenser. After 2 h, the reaction mixture is cooled and filtered. The filtrate was evaporated, the residue was dissolved in methylene chloride (2000 ml), and the solution was washed with water (2000 ml). The organic solution is evaporated, and the remaining small dissolved in denatured alcohol (1120 ml). Maleic acid (82.5 g) is added to this solution, the resulting precipitate is collected, washed with technical ethyl alcohol and dried at 55 ° C to give the title compound. 304 g) in the form of a white solid, whose structure was confirmed by spectroscopy.
    Method B (use of potassium hydroxide followed by treatment with hydrochloric acid).
    4- (2-Chlorophenyl) -3-ethoxycarbonyl-5-methoxycarbonyl-b-methyl-2- (2-phthal midoethoxy) methyl -}, 4-dihydropyridine (15 g) is dissolved in-tetrahydrofuran (150 ml ) and water (150 ml) containing potassium hydroxide (3.13 g) After stirring at room temperature for 1.5 h, 2N hydrochloric acid (100 ml) is added and the slurry is boiled under reflux 2.5 The solution is extracted twice with methylene chloride (2x100 mp), the combined extracts are dried with magnesium sulfate and evaporated. The remaining oil is dissolved in technical ethanol. maleic acid (3.24 g) is collected, the precipitate obtained is collected, washed with technical ethyl alcohol and dried at 55 ° C to obtain the title compound (10.2 g) as a gray solid, the structure of which is confirmed by spectroscopic .
    Example 18. Preparation of 4- (2-chlorophenyl) (H-methylamino) ethoxymethyl-3-ethoxycarbonyl-5-methoxy-carbonyl-6-methyl-1,4-dihydropyridine maleate.
    A mixture of (N-benzyl-K-methylamino) ethoxymethyl-4-2-chlorophenyl-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (4.8 g) and 2.2.2 trichloroethyl chlorofomyate (2.7 g) is refluxed in toluene for 20 hours. After cooling to room temperature, the mixture is stirred with 1N. hydrochloric acid (50 ml) and extracted with ether.
    Extracts evaporated. The crude oil obtained (6.9 g) contains the corresponding 2- (2- (N-2,2,2-trichloroethoxycarbonsh1-N-methylamino) ethoxymethyl derivative).
    The oil (3.0 g) was dissolved in dimethylformamide (10.5 ml) and formic acid (0.5 g), then zinc (0.7 g) was added.
    The mixture is heated to room temperature and maintained at this temperature for 3 days. The reaction mixture is then decanted, taken up in water (i 00 ml) and acidified with concentrated hydrochloric acid to. The aqueous solution was washed with n-hexane (50 ml), then 0.88 N was added. ammonia solution, which gives a precipitate. It is collected and dried, then dissolved in ethyl acetate. Maleic acid (0.34 g) is added, followed by ether. After rubbing, a solid is collected and dried, which gives a solid, the correspondence of which to the product of Example 1 is established according to NMR and infrared spectroscopy.
    Example 19. Preparation of 4- (2-chlorophenyl) (K-methylamino) ethoxy methyl 1-3-ethoxycarbonyl-5-methoxy-carbonyl-6-methyl-1., 4-dihydropyridine maleate.
    A mixture of 4- 2-chlorophenyl -2- 2- (dimethylamino) ethoxymethyl-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine. (, 6 g) and 2,2,2-trichloroethyl chloroformate ( 98.7 g) is moved in toluene at reflux for 20 h. Then the reaction mixture is cooled to room temperature and n is added. hydrochloric acid (1147 ml) The mixture is extracted twice with ether (2x1147 ml), the extracts are combined and evaporated to give a crude oil (201.6 g) containing the corresponding derivative (N-2,2,2-trichloro-lawto-carbonyl-11- methyl amino amino ethoxymethyl.
    The oil (196 g) was dissolved in dimethylformamide (686 ml) and formic acid (35.5 g), and the mixture was cooled to. Zinc (50.5 g) is added in portions over the course of 20 minutes and the mixture is moved at room temperature for 90 hours. The reaction mixture is decanted, added to water (1500 ml), then
    The pH was adjusted to pH-1 with concentrated hydrochloric acid. The aqueous solution is washed with n-hexane (500 ml) and the remaining aqueous phase is adjusted to pH 10.88 and. ammonia solution. The resulting mixture is decanted, the solid is collected and dried, which gives a crude product (138 g). This solid was dissolved in ethyl acetate, containing a minor HHOBJR acid (37.1 g), and after cooling, the compound (82.3 g) was obtained as a white solid. The identity of this substance with the product of example 18 was established by spectroscopic data.
    Similarly, the following compounds were obtained:
    2- (2-aminoethoxy) methyl-4- (2-chlorophenyl) -3-ethoxycarbonyl-5-methoxycarbonyl-6.-methyl-1, 4-dihydropyridine maleate, m.p. 169 ° C;
    2, - (2-aminoethoxy) methyl-4- (2-chlorophenyl) -3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-i, 4-dihydropyridine maleate, m.p. 169-170 ° C;
    2- | (2-aminoethoxy) methyl-4- (2,3-dichlorophene) -3-ethoxycarbonyl-5-methoxycarbonyl-6-methoxy-1,4-dihydropyridine hemi-fumarate semi-ampate, m.p. 17 73 ° C;
    2- (2-aminoethoxy) methyl-4-phenyl-3-ethoxycarbonyl-5-methoxycarbonyl-6-meth l-1, 4-dihydro pyridine fumarate hemihydrate, mp, 158-1.68 C;
    2-f (2-aminoethoxy) methyl-4- (2-fluorofen) I) -3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine fumarate, mp. 152 C.
    2- (2-aminoprop-1-hydroxymethyl) -4- (2-chlorophenyl) -3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine hemihydrate hemihydrate, i.e., 180183 C .
    The following examples illustrate the production of some starting materials.
    Example. Preparation of ethyl 4- 2- (N-benzyl-N-methyl amino ethoxy acetoacetate.
    Sodium hydride (80% in oil, 8 g), stirred in dry tetrahydrofuran (THF) (100 ml) under nitrogen, then 2-55 (N-benzyl-N-methylamino) ethanol (slowly 17g) The warm mixture is stirred for 1 h, then left in a water bath at
    , jo 5.
    20
    five
    P
     .
    five
    0
    five
    at a temperature of 20 ° C, a solution of ethyl 4-chloroacetoacetate (16.5 g) in dry THF (100 ml) is added dropwise over 3.5 hours. The mixture is stirred overnight at room temperature under nitrogen atmosphere It is then cooled by adding a small amount of ethanol and poured onto ice (100 g) and concentrated hydrochloric acid (30 ml). THF is removed by evaporation, and the residue is washed with petroleum (b.p. 60-) to remove mineral oil. The residue is basified with solid sodium carbonate and extracted with ethyl acetate (200 ml and 100 ml). The combined extracts are dried with sodium carbonate, filtered and evaporated to give the title compound as an oil (30 g), sufficiently pure for further use.
    NMR spectrum in AHSC, S values: 7.27 (5H, S); 4.12 (2H, q)} 4.06 (2H, S); 3.45-3.70 (6H, t); 2.61 (2H, t); 2.25 (3N, S); 1.23 (3N, t).
    The following acetoacetates are prepared similarly to the above method, starting from the corresponding and-substituted 2-aminoethanol and ethyl 4-chloro-I acetate.
    KgKSN2SN20CHN2OSOCH2S02S2N5, CH2Ph
    but
    where R2, -CH2. OR OR-CH CH HCH,
    Primer {) 2. Preparation of oxalic acid copium (H-benzip-N-methyl-amino) ethoxymethyl -4- (2-chlorophenyl) -3-ethoxycarbonyl-methoxycarbonip-6-methyl-1,4-dihydropyridine.
    A. Ethyl-4- 2- (L-benzyl-N-methyl-amino) ethoxy acetoacetate (25 g), 2-chlorobenzaldehyde (P g) methyl-3-amino acid (9.1 g) and acetic acid (5 ml ) in ethanol (100 ml; mixed and refluxed for 3.5 hours. The cooled reaction mixture is then evaporated to dryness and the residue is distributed between 2N hydrochloric acid (200 ml) and methylene chloride (300 ml). ml). The solution in methylene chloride is washed with a saturated carbonate solution (200 ml), dried with magnesium sulfate, filtered and evaporated to dryness. The residue in ether is triturated with an excess of oxalic acid, the solution This residue is recrystallized from methanol to give the title compound (6.5 g) as a white solid, mp 181 C.
    Found,%: C 59.42; H 5.85; N 4.39.
    C.jgH ,, Cl Ыг05 СгН ,, 04
    Calculated 7o: from 59.75; H 5.85; .N4.65.
    B. Ethyl 4- 2- (N-benzyl-H-methyl-amino) ethoxy acetoacetate (141 g) and ammonium acetate (37.3 g) in ethanol (280 mp) are carefully heated under reflux for 20 minutes. Methyl-2- (2-chloro-benzsh1dtsin) acetoacetate (115 g) is added and refluxing is continued for 4 hours. The cooled reaction mixture was evaporated to dryness, redissolved in toluene (200 ml) and extracted with 2N hydrochloric acid (2x150 ml). The oil and aqueous phase are extracted with methylene chloride (400 ml and 200 ml). The combined extracts are washed with an excess of saturated sodium carbonate solution and dried with sodium carbonate. Methylene chloride is removed by evaporation and the residue in toluene together with 20% petroleum ether is filtered under pressure through a column of silica (Merck, Kiesel - gel bon, 00 g), washed with toluene adsorbent mixed with 20% petroleum ether (500 ml) and then toluene (1 l). The combined solutions were evaporated to dryness to give the crude compound as a base, an oil (177 g), sufficiently pure according to thin layer chromatography for use in the subsequent hydrogenation step.
    Subsequent starting materials are also prepared according to method B, above, starting from the corresponding N-substituted acetoacetates and ammonium acetate.
    NZSO
    C1
     -N CH OCH2CH2N R
    NSH2R
    where R is CHJPh or
    PRI me R 3. Obtaining Ztil 4- 2- (phthalimido) ethoxy acetoacetate,
    Sodium hydride (57 wt.% - in wt. 5%, 66.1 g) is stirred in dry tetrahydrofuran (500 ml) under nitrogen atmosphere at -10. C and add L- (2-hydroxyethyl phthalamide 150 g. To this suspension, a solution of ethyl 10 4-x. Poroacetoacetate (li29.3 g) in dry tetrahydrofuran is added at -10 C for 1 h. Then the reaction the mixture is warmed to room temperature and stirring is continued for 18 hours. This mixture is taken up with t5 in N. hydrochloric acid (800 ml) and ethyl acetate (750, mp) is added. The aqueous layer is washed with ethyl acetate (300 mp) and the organic solutions are combined. washing with water (300 mp) ethyl 0 acetate evaporated to give the title compound as an oil (243 g)) sufficiently pure to give Use.
    NMR spectrum in CDCl1; 6 7.80 (4H, m);
    5 4.15 (2H, S); 4.1O (2H, q); 3.92 (2H, t); 3.78 (2H, t); 3.49 (2H, S); 1.22 (3N, t).
    Example 4. A. Preparation of 4- (2 chlorophenyl) -3-ethoxycarbonyl-5-marks-0-sycarbonyl-6-methyl-2- (2-phthalimido-ethoxy) methyl-1,4-dihydropyridine, from 2- (2-aminoethoxy ) methyl-4- (2-chlorophenyl) -3-ethoxycarbonyl-5-methoxy-carbonyl-6-methyl-1,4-dihydropyridine
    52- (2-Aminoethoxy) methyl-4- (2 chlorophenyl) -3 ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (2.0 g) and phthalic anhydride (0.73 g) stirred in acetic acid (20 ml) at reflux h. After cooling, the insoluble material was collected and stirred in methanol (10 ml). Filtering gives the specified
    in the title compound (1.0 g) as a white solid, t.pcs 146-147 C.
    Found,%: C 62.18; H 5.02; N 5.20.

    Calculated,%: C, 62.39; H 5.03; N 5.20.
    B. Preparation of the title compound from ethyl 4- 2- (phthalimido) ethoxy7-acetoacetate.
    Ethyl (phthalimido) ethoxy acetate acetate (200 g) was dissolved in isopropanol (100 ml), and to the solution of added C — T — CH OCH CH —NHR
    12-CH COjCHjCH,
    13-CHjCO-jCH
    78-80
    Butter
    Pr (favor table.1
    6.30 6.31
    (CDClg)
    5.65 5.66)
    7.72 (IH, value, broad);
    Theoretical values in brackets.
    Editor A.Dolinich
    Compiled by A. Orlov
    Tehred I. Veres Proofreader A. Zimokosov
    Order 3311/61 Circulation 379 Subscription VNIIPI USSR State Committee
    for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab., 4/5
    Production and printing company, Uzhgorod, Projecto st., 4
    - Continued that block 2
    6.96-7.51 (4H, tp); 5.43 (1H, S); 4.78 (2H, S); 4.10 (2H, q); 3.78 (3N, S); 3.63 (3N, S) i 3.3-3.7 (6H, t); 2.38 (3N, S); 1.20 (3N, t);
    Table3
    权利要求:
    Claims (5)
    [1]
    1.4- dihydropyridine of the general formula (T)
    Η V
    HsCOOcJXjpCOOCxHs h 3 c ^ C h 2 oynhr 2 n where Y is a group - (CH 2 ) 2 - or (CHjCHCHj) -;
    R, - unsubstituted phenyl or substituted with 1-2 substituents from the number of halogen, C l -C 4 -alkoxyl or hydroxy;
    R a is hydrogen, C 4 is C 4 alkyl, benzyl, 2- (C, C 4 alkoxy) ethyl or the group —CH 2 CORj, rne is an oxy group, C 9 -C 4 alkoxyl or the group is NR 4 ~ R f , where R 4 and R 5 are independently hydrogen or C 1 -C 4 -alkyl or their acid addition salts, characterized in that in the 1,4-dihydropyridine derivative of the general formula (II)
    VHjCOOCjXj-COOCiHj H 3 cd / -CHjOYX n
    where Y and R have the indicated meanings; X is a protected primary or secondary amino group, where the secondary group has the formula - N HR where is r has the indicated values with the exception of hydrogen, the protective group is removed, followed by isolation of the target product in the form of a base or an acid addition salt or by alkylation of a compound of formula (I), where Rj is hydrogen with Hal CH 2 C00 (C, C 4 -al- : kil) where Hal is chlorine or bromine, to obtain a compound of formula (I), where R z is CH 2 COO (C ^ -C ^ -alkyl), or by hydrolysis of a compound of formula (I), where R t ~ CH 2 COO (C ·, -C ¢ -alkyl), to obtain a compound of formula (I), where R 2 —CH ^ COOH, or by amination of a compound of formula (I), where R 2 is CH g of COO. (C <-C 4 -alkyl), to obtain a compound of formula (I), where R *. Is a group NR 4 R $ ·, where R 4 and Rg have the indicated meanings, followed by isolation of the target product in the form of a base or salt.
    [2]
    2. The method of pop. 1, with the fact that X is NR 2 (benzyl), where R 2 has the indicated values, or X is the group of the formula "SU < ω 1238730 AZ
    [3]
    3. The method according to claim 2, characterized in that X is NR 2 (benzyl) and the removal of the benzyl group is carried out by hydrogenation.
    [4]
    4. The method according to claim 1 ·, characterized in that X - group NR 2 SOOCH g CC1 3 and the group (SOOCH 2 CC1 5 ) are removed by exposure to zinc and formic or acetic acid.
    [5]
    5. The method of pop. 1, characterized in that the X-phthalimido and phthaloyl group are removed by exposure to methylamine, hydrazine hydrate or potassium oxide hydrate, and then hydrochloric or sulfuric acid.
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    申请号 | 申请日 | 专利标题
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