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1.发明授权Process for the asymmetric synthesis of chiral .alpha.-hydroxy-2-nitrobenzenepropanoic acid 失效手性α-羟基-2-硝基苯丙酸的不对称合成方法
公开(公告)号：US4727183A
公开(公告)日：1988-02-23
申请号：US925430
申请日：1986-10-31
IPC分类号： C07D209/42 , C07C99/00
CPC分类号： C07D209/42
摘要： Disclosed herein is a process for producing an asymmetric indoline-2-carboxylic acid of the structural Formula: ##STR1## wherein X is hydrogen, bromine, chlorine, C.sub.1-4 alkyl or C.sub.1-4 alkoxy, which comprises:(a) assymetrically reducing an o-nitrophenylpyruvic acid III by contacting the acid III with a reducing complex formed from (R)-proline or (S)-proline, respectively, and sodium borohydride in an inert solvent to form, respectively, an (S) or (R)-.alpha.-hydroxy-2-nitrobenzenepropanoic acid IV;(b) reacting, respectively, said (S) or (R)-.alpha.-hydroxy-2-nitrobenzenepropanoic acid III with a Vilsmeier chlorinating reagent in which the chlorinating agent thereof is selected from a group consisting of thionyl chloride, oxalyl chloride, phosphorus oxychloride, phosphorus pentachloride and sulfuryl chloride and the amide thereof is selected from a group consisting of dimethylformamide, diethylformamide, dimethylacetamide and diethylacetamide, said reaction being run at temperatures of at least 20.degree. C., in order to obtain, respectively, and (R) or (S)-.alpha.-chloro-2-nitrobenzenepropanoic acid IV;(c) reducing the nitro group of said (R) or (S)-.alpha.-chloro-2-nitrobenzenepropanoic acid (V) to an amino group; and(d) cyclizing the resulting (R) or (S)-.alpha.-chloro-2-aminobenzenepropanoic acid in aqueous base.
摘要翻译： 本文公开了一种制备结构式：其中X是氢，溴，氯，C 1-4烷基或C 1-4烷氧基的结构式的不对称二氢吲哚-2-羧酸的方法，其包括： （a）通过使酸III与由（R） - 脯氨酸或（S） - 脯氨酸分别形成的还原络合物和硼氢化钠在惰性溶剂中分别形成的（III）化合物分别对（ - S）或（R）-α-羟基-2-硝基苯丙酸IV; （b）分别使所述（S）或（R）-α-羟基-2-硝基苯丙酸III与Vilsmeier氯化试剂反应，其中氯化剂选自亚硫酰氯，草酰氯，磷 三氯氧化物，五氯化磷和磺酰氯，其酰胺选自二甲基甲酰胺，二乙基甲酰胺，二甲基乙酰胺和二乙基乙酰胺，所述反应在至少20℃的温度下进行，以分别得到（R ）或（S）-α-氯-2-硝基苯丙酸IV; （c）将所述（R）或（S）-α-氯-2-硝基苯丙酸（V）的硝基还原成氨基; 和（d）使得到的（R）或（S）-α-氯-2-氨基苯丙酸在碱性水溶液中环化。
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2.发明授权
公开(公告)号：US4614806A
公开(公告)日：1986-09-30
申请号：US700379
申请日：1985-02-11
IPC分类号： C07D209/42
CPC分类号： C07D209/42
摘要： Disclosed herein is a process for producing an asymmetric indoline-2-carboxylic acid of the structural Formula: ##STR1## wherein X is hydrogen, bromine, chlorine, C.sub.1-4 alkyl or C.sub.1-4 alkoxy, which comprises:(a) assymetrically reducing an o-nitrophenylpyruvic acid III by contacting the acid III with a reducing complex formed from (R)-proline or (S)-proline, respectively, and sodium borohydride in an inert solvent to form, respectively, an (S) or (R)-.alpha.-hydroxy-2-nitrobenzenepropanoic acid IV;(b) reacting, respectively, said (S) or (R)-.alpha.-hydroxy-2-nitrobenzenepropanoic acid III with a Vilsmeier chlorinating reagent in which the chlorinating agent thereof is selected from a group consisting of thionyl chloride, oxalyl chloride, phosphorus oxychloride, phosphorus pentachloride and sulfuryl chloride and the amide thereof is selected from a group consisting of dimethylformamide, diethylformamide, dimethylacetamide and diethylacetamide, said reaction being run at temperatures of at least 20.degree. C., in order to obtain, respectively, and (R) or (S)-.alpha.-chloro-2-nitrobenzenepropanoic acid IV;(c) reducing the nitro group of said (R) or (S)-.alpha.-chloro-2-nitrobenzenepropanoic acid (V) to an amino group; and(d) cyclizing the resulting (R) or (S)-.alpha.-chloro-2-aminobenzenepropanoic acid in aqueous base.
摘要翻译： 本文公开了一种制备结构式：其中X是氢，溴，氯，C 1-4烷基或C 1-4烷氧基的结构式的不对称二氢吲哚-2-羧酸的方法，其包括： （a）通过使酸III与由（R） - 脯氨酸或（S） - 脯氨酸分别形成的还原络合物和硼氢化钠在惰性溶剂中分别形成的（III）化合物分别对（ - S）或（R）-α-羟基-2-硝基苯丙酸IV; （b）分别使所述（S）或（R）-α-羟基-2-硝基苯丙酸III与Vilsmeier氯化试剂反应，其中氯化剂选自亚硫酰氯，草酰氯，磷 三氯氧化物，五氯化磷和磺酰氯，其酰胺选自二甲基甲酰胺，二乙基甲酰胺，二甲基乙酰胺和二乙基乙酰胺，所述反应在至少20℃的温度下进行，以分别得到（R ）或（S）-α-氯-2-硝基苯丙酸IV; （c）将所述（R）或（S）-α-氯-2-硝基苯丙酸（V）的硝基还原成氨基; 和（d）使得到的（R）或（S）-α-氯-2-氨基苯丙酸在碱性水溶液中环化。
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3.发明授权
公开(公告)号：US4644081A
公开(公告)日：1987-02-17
申请号：US829662
申请日：1986-02-14
IPC分类号： C07D209/42 , C07C101/447
CPC分类号： C07D209/42
摘要： Disclosed herein is a process for producing an asymmetric indoline-2-carboxylic acid of the structural Formula: ##STR1## wherein X is hydrogen, bromine, chlorine, C.sub.1-4 alkyl or C.sub.1-4 alkoxy, which comprises:(a) assymetrically reducing an o-nitrophenylpyruvic acid III by contacting the acid III with a reducing complex formed from (R)-proline or (S)-proline, respectively, and sodium borohydride in an inert solvent to form, respectively, an (S) or (R)-.alpha.-hydroxy-2-nitrobenzenepropanoic acid IV;(b) reacting, respectively, said (S) or (R)-.alpha.-hydroxy-2-nitrobenzenepropanoic acid III with a Vilsmeier chlorinating reagent in which the chlorinating agent thereof is selected from a group consisting of thionyl chloride, oxalyl chloride, phosphorus oxychloride, phosphorus pentachloride and sulfuryl chloride and the amide thereof is selected from a group consisting of dimethylformamide, diethylformamide, dimethylacetamide and diethylacetamide, said reaction being run at temperatures of at least 20.degree. C., in order to obtain, respectively, and (R) or (S)-.alpha.-chloro-2-nitrobenzenepropanoic acid IV;(c) reducing the nitro group of said (R) or (S)-.alpha.-chloro-2-nitrobenzenepropanoic acid (V) to an amino group; and(d) cyclizing the resulting (R) or (S)-.alpha.-chloro-2-aminobenzenepropanoic acid in aqueous base.
摘要翻译： 本文公开了一种制备结构式：其中X是氢，溴，氯，C 1-4烷基或C 1-4烷氧基的不对称二氢吲哚-2-羧酸的方法，其包括：（a）按比例减少 通过使酸III与由（R） - 脯氨酸或（S） - 脯氨酸分别形成的还原络合物和硼氢化钠在惰性溶剂中分别与（S）或（R（R））形成的邻硝基苯基丙酮酸III反应， ）-α-羟基-2-硝基苯丙酸IV; （b）分别使所述（S）或（R）-α-羟基-2-硝基苯丙酸III与Vilsmeier氯化试剂反应，其中氯化剂选自亚硫酰氯，草酰氯，磷 三氯氧化物，五氯化磷和磺酰氯，其酰胺选自二甲基甲酰胺，二乙基甲酰胺，二甲基乙酰胺和二乙基乙酰胺，所述反应在至少20℃的温度下进行，以分别得到（R ）或（S）-α-氯-2-硝基苯丙酸IV; （c）将所述（R）或（S）-α-氯-2-硝基苯丙酸（V）的硝基还原成氨基; 和（d）使得到的（R）或（S）-α-氯-2-氨基苯丙酸在碱性水溶液中环化。
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4.发明授权
公开(公告)号：US4585879A
公开(公告)日：1986-04-29
申请号：US700371
申请日：1985-02-11
IPC分类号： C07D209/42
CPC分类号： C07D209/42
摘要： Disclosed herein is a process for obtaining indoline-2-carboxylic acid (or derivatives thereof) comprising the following steps: (a) reducing .alpha.-oxo-2-nitrobenzenepropanoic acid to .alpha.-hydroxy-2-nitrobenzenepropanoic acid, (b) replacing the hydroxyl group of the latter with a chlorine atom utilizing a selected Vilsmeier chlorinating reagent at temperatures of at least 20.degree. C., (c) reducing the nitro group of the resulting .alpha.-chloro-2-nitrobenzenepropanoic acid to obtain .alpha.-chloro-2-aminobenzenepropanoic acid, and (d) cyclizing the latter in aqueous base to form the desired indoline-2-carboxylic acid. Alternately, steps (c) and (d) may be combined in a one pot step by using, for example, a Raney nickel-hydrazine reducing medium.
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5.发明授权Process for preparing indoline-2-carboxylic acids via .alpha.-hydroxy-2-nitrobenzenepropanoic acid 失效通过α-羟基-2-硝基苯丙酸制备二氢吲哚-2-羧酸的方法
公开(公告)号：US4645857A
公开(公告)日：1987-02-24
申请号：US829674
申请日：1986-02-14
IPC分类号： C07D209/42 , C07C101/447
CPC分类号： C07D209/42
摘要： Disclosed herein is a process for obtaining indoline-2-carboxylic acid (or derivaties thereof) comprising the following step: (a) reducing .alpha.-oxo-2-nitrobenzenepropanoic acid to .alpha.-hydroxy-2-nitrobenzenepropanoic acid, (b) replacing the hydroxyl group of the latter with a chlorine atom utilizing a selected Vilsmeier chlorinating reagent at temperatures of at least 20.degree. C., (c) reducing the nitro group of the resulting .alpha.-chloro-2-nitrobenzenepropanoic acid to obtain .alpha.-chloro-2-aminobenzenepropanoic acid, and (d) cyclizing the latter in aqueous base to form the desired indoline-2-carboxylic acid. Alternately, steps (c) and (d) may be combined in a one pot step by using, for example, a Raney nickel-hydrazine reducing medium.
摘要翻译： 本文公开了一种获得二氢吲哚-2-羧酸（或其衍生物）的方法，包括以下步骤：（a）将α-氧代-2-硝基苯丙酸还原为α-羟基-2-硝基苯丙酸，（b）将 使用选定的Vilsmeier氯化试剂，后者的羟基与氯原子在至少20℃的温度下反应，（c）还原得到的α-氯-2-硝基苯丙酸的硝基，得到α-氯-2 - 氨基苯丙酸，和（d）将其在碱水溶液中环化形成所需的二氢吲哚-2-羧酸。 或者，步骤（c）和（d）可以通过使用例如阮内镍 - 肼还原介质在一锅步骤中组合。
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6.发明授权Process for preparing indoline-2-carboxylic acids via alpha-hydroxy-2-nitrobenzenepropanoic acid 失效通过α-羟基-2-硝基苯丙酸制备二氢吲哚-2-羧酸的方法
公开(公告)号：US4785118A
公开(公告)日：1988-11-15
申请号：US925573
申请日：1986-10-31
IPC分类号： C07D209/42
CPC分类号： C07D209/42
摘要： Disclosed herein is a process for obtaining indoline-2-carboxylic acid (or derivatives thereof) comprising the following steps: (a) reducing .alpha.-oxo-2-nitrobenzenepropanoic acid to .alpha.-hydroxy-2-nitrobenzenepropanoic acid, (b) replacing the hydroxyl group of the latter with a chlorine atom utilizing a selected Vilsmeier chlorinating reagent at temperatures of at least 20.degree. C., (c) reducing the nitro group of the resulting .alpha.-chloro-2-nitrobenzenepropanoic acid to obtain .alpha.-chloro-2-aminobenzenepropanoic acid, and (d) cyclizing the latter in aqueous base to form the desired indoline-2-carboxylic acid. Alternately, steps (c) and (d) may be combined in a one pot step by using, for example, a Raney nickel-hydrazine reducing medium.
摘要翻译： 本文公开了一种获得二氢吲哚-2-羧酸（或其衍生物）的方法，包括以下步骤：（a）将α-氧代-2-硝基苯丙酸还原为α-羟基-2-硝基苯丙酸，（b）将 使用选定的Vilsmeier氯化试剂，后者的羟基与氯原子在至少20℃的温度下反应，（c）还原得到的α-氯-2-硝基苯丙酸的硝基，得到α-氯-2 - 氨基苯丙酸，和（d）将其在碱水溶液中环化形成所需的二氢吲哚-2-羧酸。 或者，步骤（c）和（d）可以通过使用例如阮内镍 - 肼还原介质在一锅步骤中组合。
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7.发明授权
公开(公告)号：US3935202A
公开(公告)日：1976-01-27
申请号：US452017
申请日：1974-03-18
IPC分类号： C07D499/00 , C07D499/46 , C07D501/20 , C07D499/44
CPC分类号： C07D499/00
摘要： The antibacterial agents of this invention present the following structural formula: ##SPC1##In whichA is a member selected from the group consisting of ##EQU1## M is a member selected from the group consisting of --H, an alkali metal and --NH.sub.4 ; andY is a member selected from the group consisting of ##EQU2## wherein R is --H, alkanoyloxy of 2 to 6 carbon atoms, ##SPC2##Or,When taken with the 3-carboxy group, ##SPC3##.
摘要翻译： 本发明的抗菌剂具有以下结构式：
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8.发明授权N-(2-Substituted-1-oxoalkyl)-2,3-dihydro-1H-indole-2-carboxylic acid derivatives 失效N-（2-取代的-1-氧代烷基）-2,3-二氢-1H-吲哚-2-羧酸衍生物
公开(公告)号：US4454291A
公开(公告)日：1984-06-12
申请号：US391080
申请日：1982-06-22
申请人： Dong H. Kim , Ronald J. McCaully
发明人： Dong H. Kim , Ronald J. McCaully
IPC分类号： C07D209/42 , C07D513/04
CPC分类号： C07D513/04 , C07D209/42 , Y02P20/55
摘要： Disclosed herein are 2,3-dihydro-1H-indole-2-carboxylic acids substituted on the nitrogen with 3-mercapto-2-alkyl-1-oxoalkyl, 3-phosphoryl-2-alkyl-1-oxopropyl, or 2-amino-2-alkyl-1-oxoalkyl derivatives which act as inhibitors of angiotensin converting enzyme and as antihypertensive agents. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0;R.sub.1 is hydrogen, lower alkyl, aryl or aralkyl;R.sub.2 is hydrogen or lower alkyl;R.sub.3 is hydrogen, lower alkyl or aroyl;R.sub.5 is hydroxy, amino, or lower alkoxy;X is hydrogen, hydroxy, lower alkyl, lower alkoxy, or halogen;Y is hydrogen, lower alkyl, or aryl;Y is hydrogen, lower alkyl, or aryl;R.sub.4 is ##STR2## wherein: L is O, NR.sub.7 or S (where R.sub.7 is hydrogen or lower alkyl);M is R.sub.8, OR.sub.8, SR.sub.8, or NR.sub.9 R.sub.10 (where R.sub.8 is hydrogen, lower alkyl, aryl, or aralkyl; and R.sub.9 and R.sub.10 are, independently, hydrogen, lower alkyl, or aryl);A is O, NR.sub.13 or S;R.sub.11 and R.sub.12 are, independently, hydrogen, alkyl, aralkylor aryl;R.sub.13 is hydrogen or lower alkyl;m is 0, 1, 2, or 3;R.sub.20 is hydrogen or aryl; andR.sub.21 is hydroxy or lower alkoxy; or pharmaceutically acceptable salts thereof.Claimed compounds are intermediates of the formula: ##STR3## wherein R.sub.13 is hydrogen or lower alkyl; R.sub.14 is R.sub.5 or OZ, where R.sub.5 is hydroxy, amino, or lower alkoxy, and Z is a carboxylic acid protecting group.
摘要翻译： 本文公开了在氮上与3-巯基-2-烷基-1-氧代烷基，3-磷酰基-2-烷基-1-氧代丙基或2-氨基取代的2,3-二氢-1H-吲哚-2-羧酸 -2-烷基-1-氧代烷基衍生物，其作为血管紧张素转化酶的抑制剂和抗高血压药。 本发明的化合物（不包括所公开的中间体）具有以下通式：其中n为1或0; R1是氢，低级烷基，芳基或芳烷基; R2是氢或低级烷基; R3是氢，低级烷基或芳酰基; R5是羟基，氨基或低级烷氧基; X是氢，羟基，低级烷基，低级烷氧基或卤素; Y是氢，低级烷基或芳基; Y是氢，低级烷基或芳基; R 4是O，NR 7或S（其中R 7是氢或低级烷基）; M是R 8，OR 8，SR 8或NR 9 R 10（其中R 8是氢，低级烷基，芳基或芳烷基;且R 9和R 10独立地是氢，低级烷基或芳基）。 A为O，NR 13或S; R 11和R 12独立地为氢，烷基，芳烷基或芳基; R 13是氢或低级烷基; m为0,1,2或3; R 20是氢或芳基; 和R 21是羟基或低级烷氧基; 或其药学上可接受的盐。 所要求的化合物是下式的中间体：其中R 13是氢或低级烷基; R14是R5或OZ，其中R5是羟基，氨基或低级烷氧基，Z是羧酸保护基。
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9.发明授权N-(2-Substituted-1-oxoalkyl)-2,3-dihydro-1H-indole-2-carboxylic acid derivatives 失效N-（2-取代的-1-氧代烷基）-2,3-二氢-1H-吲哚-2-羧酸衍生物
公开(公告)号：US4350633A
公开(公告)日：1982-09-21
申请号：US284433
申请日：1981-07-20
申请人： Dong H. Kim , Ronald J. McCaully
发明人： Dong H. Kim , Ronald J. McCaully
IPC分类号： C07D209/42 , C07D513/04 , C07D209/04
CPC分类号： C07D513/04 , C07D209/42
摘要： Disclosed herein are 2,3-dihydro-1H-indole-2-carboxylic acids substituted on the nitrogen with 3-mercapto-2-alkyl-1-oxoalkyl, 3-phosphoryl-2-alkyl-1-oxopropyl, or 2-amino-2-alkyl-1-oxoalkyl derivatives which act as inhibitors of angiotensin converting enzyme and as antihypertensive agents. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0;R.sub.1 is hydrogen, lower alkyl, aryl or aralkyl;R.sub.2 is hydrogen or lower alkyl;R.sub.3 is hydrogen, lower alkyl or aroyl;R.sub.5 is hydroxy, amino, or lower alkoxy;X is hydrogen, hydroxy, lower alkyl, lower alkoxy, or halogen;Y is hydrogen, lower alkyl, or aryl;Y is hydrogen, lower alkyl, or aryl;R.sub.4 is ##STR2## wherein: L is O, NR.sub.7 or S (where R.sub.7 is hydrogen or lower alkyl);M is R.sub.8, OR.sub.8, SR.sub.8, or NR.sub.9 R.sub.10 (where R.sub.8 is hydrogen, lower alkyl, aryl, or aralkyl; and R.sub.9 and R.sub.10 are, independently, hydrogen, lower alkyl, or aryl);A is O, NR.sub.13 or S;R.sub.11 and R.sub.12 are, independently, hydrogen, alkyl, aralkyl or aryl;R.sub.13 is hydrogen or lower alkyl;m is 0, 1, 2, or 3;R.sub.20 is hydrogen or aryl; andR.sub.21 is hydroxy or lower alkoxy;or pharmaceutically acceptable salts thereof.
摘要翻译： 本文公开了在氮上与3-巯基-2-烷基-1-氧代烷基，3-磷酰基-2-烷基-1-氧代丙基或2-氨基取代的2,3-二氢-1H-吲哚-2-羧酸 -2-烷基-1-氧代烷基衍生物，其作为血管紧张素转化酶的抑制剂和抗高血压药。 本发明的化合物（不包括所公开的中间体）具有以下通式：其中n为1或0; R1是氢，低级烷基，芳基或芳烷基; R2是氢或低级烷基; R3是氢，低级烷基或芳酰基; R5是羟基，氨基或低级烷氧基; X是氢，羟基，低级烷基，低级烷氧基或卤素; Y是氢，低级烷基或芳基; Y是氢，低级烷基或芳基; R 4是O，NR 7或S（其中R 7是氢或低级烷基）; M是R 8，OR 8，SR 8或NR 9 R 10（其中R 8是氢，低级烷基，芳基或芳烷基;且R 9和R 10独立地是氢，低级烷基或芳基）。 A为O，NR 13或S; R 11和R 12独立地为氢，烷基，芳烷基或芳基; R 13是氢或低级烷基; m为0,1,2或3; R 20是氢或芳基; 和R 21是羟基或低级烷氧基; 或其药学上可接受的盐。
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公开(公告)号：US4349674A
公开(公告)日：1982-09-14
申请号：US970295
申请日：1978-12-18
IPC分类号： C07D241/44 , C07D241/42 , A61K31/495 , C07D401/12
CPC分类号： C07D241/44
摘要： The compounds of this invention are designated as quinoxalinyl esters of carbamimidothioic acids and exhibit the pharmacological properties of preventing gastric ulcers, reducing gastric secretions and lowering blood pressure. The compounds have the following structural formula: ##STR1## in which Q is hydrogen or nitro;A is hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, carbomethoxy, carbethoxy, carbopropoxy, carbisopropoxy, carbobutoxy, carbisobutoxy, or carbo-t-butoxy; andR.sup.1, R.sup.2, and R.sup.3 are, independently, hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, t-butyl, allyl, or R.sup.1 and R.sup.3 may be concatenated with a carbon chain having 4 carbon atoms with R.sup.2 then being hydrogen; except that, when A and Q are hydrogen, R.sup.1, R.sup.2, and R.sup.3 may not all be hydrogen; and with the further exception that, where A is methyl and R.sup.1, R.sup.2, and Q are all hydrogen, R.sup.3 may not be ethyl;or a pharmaceutically acceptable salt thereof.
摘要翻译： 本发明的化合物被指定为氨基亚氨基硫酸的喹喔啉基，并且具有预防胃溃疡，减少胃分泌和降低血压的药理学特性。 该化合物具有以下结构式：其中Q是氢或硝基的
A是氢，甲基，乙基，丙基，异丙基，正丁基，甲酯基，乙酯基，碳丙氧基，碳异丙氧基，羰基丁氧基，碳代异丁氧基或碳 - 并且R 1，R 2和R 3独立地是氢，甲基，乙基，丙基，异丙基，正丁基，异丁基，叔丁基，烯丙基，或者R 1和R 3可以与具有4个碳原子的碳链连接在一起 然后是氢; 除了当A和Q为氢时，R 1，R 2和R 3可以不全部为氢; 并且另外例外的是，当A是甲基且R 1，R 2和Q都是氢时，R 3可以不是乙基; 或其药学上可接受的盐。
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