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【结 构 式】

【分子编号】10264

【品名】1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione

【CA登记号】6066-82-6

【 分 子 式 】C4H5NO3

【 分 子 量 】115.08864

【元素组成】C 41.75% H 4.38% N 12.17% O 41.71%
与该中间体有关的原料药合成路线共 19 条
合成路线1合成路线2合成路线3合成路线4合成路线5合成路线6合成路线7合成路线8合成路线9合成路线10合成路线11合成路线12合成路线13合成路线14合成路线15合成路线16合成路线17合成路线18合成路线19

合成路线1

该中间体在本合成路线中的序号：(IV)

The reaction of 2-amino-3-(N-methylcarbamoyl)propionic acid (I) with 2-nitrophenylsulfonylchloride (II) by means of K2CO3 in THF gives 2-(2-nitrophenylsulfonylamino)-3-(N-methylcarbamoyl)propionic acid (III), which is esterified with N-hydroxysuccinimide (IV) by means of dicyclohexylcarbodiimide in THF yielding the corresponding N-succinimido ester (V). The condensation of (V) with amoxicillin [6-[alpha-amino-alpha-(4-hydroxyphenyl)acetylamino]penicillanic acid] (VI) by means of triethylamine in THF-CHCl3 affords 6-[alpha[2-(2-nitrophenylsulfonylamino)-3-N-methylcarbamoylpropionamido]-alpha-(4-hydroxyphenyl)acetamido]penicillanic acid (VII). Finally, the sulfonic group is eliminated by treatment with thiobenzamide (A) in ethanol-THF.

参考文献 中间体
合成目标
【1】 Kawazu, M.; et al. (Tanabe Seiyaku Co., Ltd.); Penicillins and processes for preparing the same. DE 2638067; FR 2323384; NL 7610151; US 4053609 .
【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; TA-058. Drugs Fut 1980, 5, 3, 151.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 32629 Thiobenzamide; Benzenecarbothioamide 2227-79-4 C7H7NS 详情 详情
(I) 32623 (2R)-2-amino-3-(N-methylcarbamoyl)propionic acid; (2R)-2-amino-4-(methylamino)-4-oxobutyric acid C5H10N2O3 详情 详情
(II) 32624 2-Nitrobenzenesulfonyl chloride 1694-92-4 C6H4ClNO4S 详情 详情
(III) 32625 (2R)-2-(2-nitrophenylsulfonylamino)-3-(N-methylcarbamoyl)propionic acid; (2R)-4-(methylamino)-2-[[(2-nitrophenyl)sulfonyl]amino]-4-oxobutyric acid C11H13N3O7S 详情 详情
(IV) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(V) 32626 (3R)-4-[(2,5-dioxo-1-pyrrolidinyl)oxy]-N-methyl-3-[[(2-nitrophenyl)sulfonyl]amino]-4-oxobutanamide C15H16N4O9S 详情 详情
(VI) 32627 6-[alpha-amino-alpha-(4-hydroxyphenyl)acetamido]penicillanic acid; Amoxicillin; (2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)ethanoyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid 26787-78-0 C16H19N3O5S 详情 详情
(VII) 32628 (2S,5R,6R)-6-([(2R)-2-(4-hydroxyphenyl)-2-[((2R)-4-(methylamino)-2-[[(2-nitrophenyl)sulfonyl]amino]-4-oxobutanoyl)amino]ethanoyl]amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 6-[alpha[2-(2-nitrophenylsulfonylamino)-3-N-methylcarbamoylpropionamido]-alpha-(4-hydroxyphenyl)acetamido]penicillanic acid C27H30N6O11S2 详情 详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

Antineopleston A10 (A10) can be obtained by two different ways: 1) A10 has been synthesized in two steps: Condensation of phenylacetic acid (I) with L-glutamine (V) to give phenylacetyl-L-glutamine (VI), followed by intramolecular cyclization of the latter. In the first step (I) is activated by reacting with various reagents such as HOSu (N-hydroxysuccinimide) (II) in the presence of DCC, DCC (N,N-dicyclohexylcarbodiimide) or 2-mercaptothiazoline (III) in the presence of DCC to afford the intermediates (IVa), (IVb) and (IVc), respectively. Without isolation, the intermediate (IVa), (IVb) or (IVc) is treated with a solution of L-glutamine in CH3CN:H2O (2:1) containing NaHCO3 to give (VI) in 60, 87 and 82% yields, respectively. In the second step (VI) is converted to the activated intermediate (IXa) or (IXb) by treatment with CDI (1,1'-carbonydiimidazole) (VII) or HOSu (VIII) in the presence of DCC. Finally, intramolecular cyclization of (IXa) or (IXb) is effected by treating the latter at 80 C to yield A10 in 85 or 82% yield, respectively. 2) Reaction of phenylacetyl chloride with L-glutamine in aqueous solution containing NaHCO3 affords phenylacetyl-L-glutamine (VI), which is heated at 160 C to give A10.

参考文献 中间体
合成目标
【1】 Verhoef, J.; Schmitz, F.-J.; Fluit, A.C.; Milatovic, D.; 13th Intl Cong Chemother (Aug. 28-Sept. 2, Vienna) 1983, 50, 2, PS 12.4-11-4.
【2】 Burzynski, S.R. (Burzynski Research Institute); Purified antineoplaston factions and methods of treating neoplastic disease. EP 0069232; JP 5032548; JP 5058886; JP 58010521; US 4470970 .
【3】 Burzynski, S.R.; Hai, T.T.; Antineoplaston A10. Drugs Fut 1985, 10, 2, 103.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
10101 Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene 501-53-1 C8H7ClO2 详情 详情
(IVa) 24947 1-[(2-phenylacetyl)oxy]-2,5-pyrrolidinedione C12H11NO4 详情 详情
(IVb) 28896 phenylacetic anhydride C16H14O3 详情 详情
(IVc) 28897 2-phenyl-1-(2-thioxo-1,3-thiazolidin-3-yl)-1-ethanone C11H11NOS2 详情 详情
(IXa) 28899 (3S)-4-(1H-imidazol-1-yl)-4-oxo-3-[(2-phenylacetyl)amino]butanamide C15H16N4O3 详情 详情
(IXb) 28900 (3S)-4-[(2,5-dioxo-1-pyrrolidinyl)oxy]-4-oxo-3-[(2-phenylacetyl)amino]butanamide C16H17N3O6 详情 详情
(I) 16148 Benzeneacetic acid; 2-Phenylacetic acid; Phenyl Acetic Acid 103-82-2 C8H8O2 详情 详情
(II) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(III) 28895 4,5-dihydro-1,3-thiazol-2-ylhydrosulfide 96-53-7 C3H5NS2 详情 详情
(V) 24948 L-glutamine 56-85-9 C5H10N2O3 详情 详情
(VI) 28898 (2S)-4-amino-4-oxo-2-[(2-phenylacetyl)amino]butyric acid C12H14N2O4 详情 详情
(VII) 11353 1,1'-Carbonyldiimidazole; Di(1H-imidazol-1-yl)methanone; N,N-Carbonyldiimidazole; 1,1'-Carbonylbis(1H-imidazole) 530-62-1 C7H6N4O 详情 详情
(VIII) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情

合成路线3

该中间体在本合成路线中的序号：(II)

Antineopleston A10 (A10) can be obtained by two different ways: 1) A10 has been synthesized in two steps: Condensation of phenylacetic acid (I) with L-glutamine (V) to give phenylacetyl-L-glutamine (VI), followed by intramolecular cyclization of the latter. In the first step (I) is activated by reacting with various reagents such as HOSu (N-hydroxysuccinimide) (II) in the presence of DCC, DCC (N,N-dicyclohexylcarbodiimide) or 2-mercaptothiazoline (III) in the presence of DCC to afford the intermediates (IVa), (IVb) and (IVc), respectively. Without isolation, the intermediate (IVa), (IVb) or (IVc) is treated with a solution of L-glutamine in CH3CN:H2O (2:1) containing NaHCO3 to give (VI) in 60, 87 and 82% yields, respectively. In the second step (VI) is converted to the activated intermediate (IXa) or (IXb) by treatment with CDI (1,1'-carbonydiimidazole) (VII) or HOSu (VIII) in the presence of DCC. Finally, intramolecular cyclization of (IXa) or (IXb) is effected by treating the latter at 80 C to yield A10 in 85 or 82% yield, respectively. 2) Reaction of phenylacetyl chloride with L-glutamine in aqueous solution containing NaHCO3 affords phenylacetyl-L-glutamine (VI), which is heated at 160 C to give A10.

参考文献 中间体
合成目标
【1】 Verhoef, J.; Schmitz, F.-J.; Fluit, A.C.; Milatovic, D.; 13th Intl Cong Chemother (Aug. 28-Sept. 2, Vienna) 1983, 50, 2, PS 12.4-11-4.
【2】 Burzynski, S.R. (Burzynski Research Institute); Purified antineoplaston factions and methods of treating neoplastic disease. EP 0069232; JP 5032548; JP 5058886; JP 58010521; US 4470970 .
【3】 Burzynski, S.R.; Hai, T.T.; Antineoplaston A10. Drugs Fut 1985, 10, 2, 103.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
10101 Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene 501-53-1 C8H7ClO2 详情 详情
(IVa) 24947 1-[(2-phenylacetyl)oxy]-2,5-pyrrolidinedione C12H11NO4 详情 详情
(IVb) 28896 phenylacetic anhydride C16H14O3 详情 详情
(IVc) 28897 2-phenyl-1-(2-thioxo-1,3-thiazolidin-3-yl)-1-ethanone C11H11NOS2 详情 详情
(IXa) 28899 (3S)-4-(1H-imidazol-1-yl)-4-oxo-3-[(2-phenylacetyl)amino]butanamide C15H16N4O3 详情 详情
(IXb) 28900 (3S)-4-[(2,5-dioxo-1-pyrrolidinyl)oxy]-4-oxo-3-[(2-phenylacetyl)amino]butanamide C16H17N3O6 详情 详情
(I) 16148 Benzeneacetic acid; 2-Phenylacetic acid; Phenyl Acetic Acid 103-82-2 C8H8O2 详情 详情
(II) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(III) 28895 4,5-dihydro-1,3-thiazol-2-ylhydrosulfide 96-53-7 C3H5NS2 详情 详情
(V) 24948 L-glutamine 56-85-9 C5H10N2O3 详情 详情
(VI) 28898 (2S)-4-amino-4-oxo-2-[(2-phenylacetyl)amino]butyric acid C12H14N2O4 详情 详情
(VII) 11353 1,1'-Carbonyldiimidazole; Di(1H-imidazol-1-yl)methanone; N,N-Carbonyldiimidazole; 1,1'-Carbonylbis(1H-imidazole) 530-62-1 C7H6N4O 详情 详情
(VIII) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情

合成路线4

该中间体在本合成路线中的序号：(V)

The synthesis of racemic 15-deoxyspergualin and tritium-labeled compound has been described: The oxidation of N-(3-hydroxypropyl)carbamic acid tert-butyl ester (I) with pyridinium chlorochromate in dichloromethane gives N-(3-oxopropyl)carbamic acid tert-butyl ester (II), which is condensed with 4-(triphenylphosphonium)butyrate (III) by means of lithium bis(trimethylsilyl)amide in THF yielding 7-(tert-butoxycarbonylamino)-4-heptenoic acid (IV). The esterification of (IV) with N-hydroxysuccinimide (V) by means of dicyclohexylcarbodiimide and 1-hydroxybenzotriazole affords the corresponding ester (VI), which is treated with ammonia in methanol giving the corresponding amide (VII). The hydrolysis of (VII) with HCl in ethyl acetate yields 7-amino-4-heptenamide (VIII), which is treated with 3,5-dimethylpyrazole-1-carboxamidine (IX) and K2CO3 in methanol affording 7-guanidino-4-heptenamide (X). The reduction of (X) gives 7-guanidinoheptanamide (XI), which is finally condensed with glyoxylspermidine (XII) by means of glutaric acid in hot water. The tritium-labeled compound can also be obtained in the same way by performing the reduction of heptenamide (X) with tritium gas.

参考文献 中间体
合成目标
【1】 Cook, D.J.; Tepper, M.A.; Saulnier, M.G.; Dischino, D.D.; Synthesis of tritium labeled (±) 15-deoxyspergualin trihydrochloride. J Label Compd Radiopharm 1993, 33, 2, 137.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 10260 tert-butyl N-(3-hydroxypropyl)carbamate 58885-58-8 C8H17NO3 详情 详情
(II) 10261 tert-butyl N-(3-oxopropyl)carbamate C8H15NO3 详情 详情
(III) 10262 4-(triphenylphosphonio)butanoate C22H22O2P 详情 详情
(IV) 10263 (E)-7-[(tert-Butoxycarbonyl)amino]-4-heptenoic acid C12H21NO4 详情 详情
(V) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(VI) 10265 tert-butyl N-[(E)-7-[(2,5-dioxo-1-pyrrolidinyl)oxy]-7-oxo-3-heptenyl]carbamate C16H24N2O6 详情 详情
(VII) 10266 tert-butyl N-[(E)-7-amino-7-oxo-3-heptenyl]carbamate C12H22N2O3 详情 详情
(VIII) 10267 (E)-7-Amino-4-heptenamide C7H14N2O 详情 详情
(IX) 10268 3,5-Dimethyl-1H-pyrazole-1-carboximidamide C6H10N4 详情 详情
(X) 10269 (E)-7-[[Amino(imino)methyl]amino]-4-heptenamide C8H16N4O 详情 详情
(XI) 10270 7-[[Amino(imino)methyl]amino]heptanamide C8H18N4O 详情 详情
(XI) 44635 7-[[amino(imino)methyl]amino]heptanamide C8H18N4O 详情 详情
(XII) 10271 N-[4-[(3-Aminopropyl)amino]butyl]-2,2-dihydroxyacetamide C9H21N3O3 详情 详情

合成路线5

该中间体在本合成路线中的序号：(II)

1) The esterification of N-acetylmuramyl-L-alanyl-D-glutaminyl-L-alanine (I) with N-hydroxysuccinimide (II) by means of dicyclohexylcarbodiimide in dimethylacetamide gives the corresponding N-hydroxysuccinimide ester (III), which is then to condensed with O-(1,2-dipalmitoyl-sn-glycero-3-phosphoryl)ethanolamine (IV) by means of triethylamine in the same solvent.

参考文献 中间体
合成目标
【1】 Baschang, G.; Carcsay, L.; Hartmann, A.; Stanek, J. (Novartis AG); Phosphorylmuramyl peptides, process for their preparation and use. EP 0027258 .
【2】 Slusarchyk, W.A.; Dejneka, T.; Kostes, W.H. (Bristol-Myers Squibb Co.); Preparation of 4,4-dialkyl-2-azetidinones. AU 8652460; BE 090411; DE 3602347; ES 8706112; ES 8800897; FR 2576596; GB 2170201; US 4638061 .
【3】 Prous, J.; Castaner, J.; ENV 2-3/MTP-PE. Drugs Fut 1989, 14, 3, 220.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 20523 N-[4-([2-[(2-[[3-(acetamido)-2,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy]propanoyl)amino]propanoyl]amino)-5-amino-5-oxopentanoyl]alanine C22H37N5O12 详情 详情
(II) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(III) 20525 2-([2-[(2-[[3-(acetamido)-2,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy]propanoyl)amino]propanoyl]amino)-N(5)-[2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-1-methyl-2-oxoethyl]pentanediamide C26H40N6O14 详情 详情
(IV) 20526 2-[[(2-aminoethoxy)(hydroxy)phosphoryl]oxy]-1-[(palmitoyloxy)methyl]ethyl palmitate 923-61-5 C37H74NO8P 详情 详情

合成路线6

该中间体在本合成路线中的序号：(II)

2) The esterification of N-acetyl-L-alanyl-D-glutamine (V) with N-hydroxysuccinimide (II) as before gives the corresponding N-hydroxysuccinimide ester (VI), which is then condensed with N-alanyl-O-(1,2-dipalmitoyl-sn-glycero-3-phosphoryl)ethanolamine (VII) by means of triethylamine as before.

参考文献 中间体
合成目标
【1】 Prous, J.; Castaner, J.; ENV 2-3/MTP-PE. Drugs Fut 1989, 14, 3, 220.
【2】 Brundish, D.E.; Wade, R.; Synthesis of N-[2-3H]acetyl-D-muramyl-L-alanyl-D-iso-glutaminyl-L-alanyl-2-(1', 2'-dipalmitoyl-sn-glycero-3'-phosphoryl)ethylamide of high specific radioactivity. J Label Compd Radiopharm 1985, 22, 1, 29-35.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(II) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(V) 20527 4-([2-[(2-[[3-(acetamido)-2,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy]propanoyl)amino]propanoyl]amino)-5-amino-5-oxopentanoic acid 53678-77-6 C19H32N4O11 详情 详情
(VI) 20528 2-([2-[(2-[[3-(acetamido)-2,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy]propanoyl)amino]propanoyl]amino)-5-[(2,5-dioxo-1-pyrrolidinyl)oxy]-5-oxopentanamide C23H35N5O13 详情 详情
(VII) 20529 10-amino-4-hydroxy-4,9-dioxo-2-(palmitoyloxy)-3,5-dioxa-8-aza-4lambda(5)-phosphaundec-1-yl palmitate C39H77N2O9P 详情 详情

合成路线7

该中间体在本合成路线中的序号：(V)

This compound can be obtained in three similar ways: 1) The reaction of N-acetyl-L-methionine (I) with ethyl chloroformate (II) and triethylamine in chloroform gives the corresponding mixed anhydride (III), which is then condensed with 3,4-di(ethoxycarbonyloxy)phenethylamine tosylate (IV) by means of triethylamine in chloroform. 2) The reaction of N-acetyl-L-methionine (I) with N-hydroxysuccinimide (V) by means of dicyclohexylcarbodiimide (DDC) in dioxane gives the corresponding active ester (VI), which is then condensed with the amine (IV) as before. The active ester method can also be carried out in this case using N-hydroxyphthalimide, 1-hydroxybenzothiazole or 4-nitrophenol instead of N-hydroxysuccinimide (V). 3) The reaction of the active ester (VI) with dopamine (VII) by means of triethylamine in DMF gives the corresponding amide (VIII), which is then acylated with ethyl chloroformate (IX) in pyridine.

参考文献 中间体
合成目标
【1】 Kiguchi, T.; Hatashi, K.; Yamaguchi, I. (Tanabe Seiyaku Co., Ltd.); Phenethylamine derivs., process for preparing same and pharmaceutical compositions containing said phenethylamine derivs. EP 0007441; JP 1980007242 .
【2】 Prous, J.; Castaner, J.; DOCARPAMINE. Drugs Fut 1990, 15, 2, 122.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
60593 p-xylene C8H10 详情 详情
(II), (IX) 11229 1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate 541-41-3 C3H5ClO2 详情 详情
(I) 11228 (2S)-2-(Acetamido)-4-(methylsulfanyl)butyric acid 65-82-7 C7H13NO3S 详情 详情
(III) 11230 N-Acetyl-L-methionine ethoxycarbonyl anhydride C10H17NO5S 详情 详情
(IV) 11231 4-(2-aminoethyl)-2-[(ethoxycarbonyl)oxy]phenyl ethyl carbonate C14H19NO6 详情 详情
(V) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(VI) 11233 N-[(1S)-1-[[(2,5-Dioxo-1-pyrrolidinyl)oxy]carbonyl]-3-(methylsulfanyl)propyl]acetamide C11H16N2O5S 详情 详情
(VII) 11234 4-(2-Aminoethyl)-1,2-benzenediol 51-61-6 C8H11NO2 详情 详情
(VIII) 11235 (2S)-2-(Acetamido)-N-(3,4-dihydroxyphenethyl)-4-(methylsulfanyl)butanamide 122570-36-9 C15H22N2O4S 详情 详情

合成路线8

该中间体在本合成路线中的序号：(B)

Antineoplaston AS2-5 (AS2-5) can be obtained in the following way (1,2): N-Phenylacetyl-L-glutamine sodium is synthesized in two steps. In the first step, phenylacetic acid (I) is treated with N-hydroxysuccinimide (B) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (A) in acetonitrile to give intermediate (Ia). In the second step, (Ia) is reacted without purification with L-glutamine (II) in the presence of NaHCO3 in 1:1 acetonitrile-water mixture to afford N-phenylacetyl-L-glutamine (III) in 87% yield. Compound (III) is then converted to sodium salt in aqueous solution by treatment with aqueous sodium hydroxide solution (pH 7). In a large scale preparation reaction of phenylacetyl chloride with L-glutamine in aqueous solution containing NaHCO3 affords N-phenyiacetyl L-glutamine sodium.

参考文献 中间体
合成目标
【1】 Burzynski, S.R. (Burzynski Research Institute); Purified antineoplaston fractions and methods of treating neoplastic disease. US 4558057 .
【2】 Berman, E.M.; Gregor, V.E.; Showalter, H.H.D. (Pfizer Inc.); Benzoselenino[4,3,2-cd]indazole compound, compositions comprising the compounds and processes for producing the compounds. AU 8544154; EP 0170412; ES 8704956 .
【3】 Khalid, M.; Burzynski, S.R.; Antineoplaston AS2-5. Drugs Fut 1986, 11, 5, 364.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(B) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(Ia) 24927 tert-butyl (2R,3aR,7aR,10aR)-8-(dimethoxymethyl)-5-(5-hexenyl)-10-oxo-2-vinyl-2,3,5,6,7,7a,10,10a-octahydropyrrolo[2,3-i]isoquinoline-1(4H)-carboxylate C27H42N2O5 详情 详情
(A) 24945 N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide 25952-53-8 C8H17N3 详情 详情
(I) 16148 Benzeneacetic acid; 2-Phenylacetic acid; Phenyl Acetic Acid 103-82-2 C8H8O2 详情 详情
(II) 24948 L-glutamine 56-85-9 C5H10N2O3 详情 详情
(III) 24949 (2S)-5-amino-5-oxo-2-[(2-phenylacetyl)amino]pentanoic acid C13H16N2O4 详情 详情

合成路线9

该中间体在本合成路线中的序号：

This compound can be obtained by two related ways: 1) The condensation of 2-O-(p-toluenesulfonyl)-D-lactoyl chloride (IV) with 1-methyl-2-oxoimidazolidine-4(S)-carboxylic acid tert-butyl ester (VIII) by means of potassium tert-butoxide in THF gives 1-methyl-2-oxo-3-[2(R)-(p-toluenesulfonyloxy)propionyl]imidazolidine-4(S)-carboxylic acid tert-butyl ester (IX), which is then condensed with 2(S)-amino-4-phenylbutyric acid ethyl ester (X) by means of triethylamine in DMSO yielding 3-[N-[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-1-methyl-2-oxoimidazolidine-4(S)-carboxylic acid tert-butyl ester (XI). Finally, this compound is hydrolyzed with HCl in dioxane - water. The starting compounds (IV) and (VIII) are obtained as follows: a) The condensation of D-lactic acid methyl ester with p-toluenesulfonyl chloride and triethylamine gives the corresponding sulfonate (II), which is hydrolyzed with NaOH to the free acid (III). Finally, this compound is treated with refluxing SOCl2 to give acid chloride (IV). b) The esterification of 3-(benzyloxycarbonyl)-2-oxoimidazolidine-4(S)-carboxylic acid (V) with tert-butanol gives the corresponding ester (VI), which is methylated with methyl iodide and K2CO3 to 3-(benzyloxycarbonyl)-1-methyl-2-oxoimidazolidine-4(S)-carboxylic acid tert-butyl ester (VII). This compound is debenzylated by hydrogenation with H2 over Pd/C to afford imidazolidine ester (VIII). 2) The condensation of 2(S)-bromo-4-phenylbutyric acid ethyl ester (XII) with L-alanine benzyl ester (XIII) by means of K2CO3 in DMSO gives N-[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine benzyl ester (XIV), which is debenzylated by hydrogenation as before yielding the free acid (XV). The esterification of (XV) with N-hydroxysuccinimide gives the corresponding active ester (XVI), which is finally condensed with imidazolidine ester (VIII) by means of potassium tert-butoxide to afford the precursor (XI) already obtained.

参考文献 中间体
合成目标
【1】 Yoneda, N.; Kato, S.; Hayashi, K.; Ochiai, K. (Tanabe Seiyaku Co., Ltd.); Agents for the treatment of hypertension. JP 1985013715 .
【2】 Yoneda, N.; Kato, J.; Hayashi, K.; Ochiani, T.; Kinashi, K. (Tanabe Seiyaku Co., Ltd.); Quinolinecarboxylic acid derivs. and method for their preparation. EP 0095163; ES 8603427; US 4508727 .
【3】 Hayashi, K.; Kubota, H. (Tanabe Seiyaku Co., Ltd.); Process for preparing optically active 2-oxoimidazolidine derivs. EP 0373881 .
【4】 Kato, J.; Hayashi, K.; Ishida, R.; Yoneda, N.; Ochiai, T.; Kubo, M.; Nunami, K.-I.; Studies on angiotensin converting enzyme inhibitors. 4. Synthesis and angiotensin converting enzyme inhibitory activities of 3-acyl-1-alkyl-2-oxoimidazolidine-4-carboxylic acid derivatives. J Med Chem 1989, 32, 2, 289.
【5】 Hayashi, K.; Kubota, H.; Yamagishi, M.; Nunami, K.-I.; Nishimoto, S.; Studies on angiotensin converting enzyme inhibitors. V. The diastereoselective synthesis of 2-oxoimidazolidine derivatives. Chem Pharm Bull 1991, 39, 6, 1374.
【6】 Prous, J.; Castaner, J.; Imidapril Hydrochloride. Drugs Fut 1992, 17, 7, 551.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(I) 11591 methyl (2R)-2-hydroxypropanoate 17392-83-5 C4H8O3 详情 详情
(II) 15653 Methyl (2S)-2-{[(4-methylphenyl)sulfonyl]oxy}propanoate C11H14O5S 详情 详情
(III) 15654 (2R)-2-[[(4-methylphenyl)sulfonyl]oxy]propionic acid C10H12O5S 详情 详情
(IV) 15655 (1R)-2-chloro-1-methyl-2-oxoethyl 4-methylbenzenesulfonate C10H11ClO4S 详情 详情
(V) 15656 (4S)-3-[(benzyloxy)carbonyl]-2-oxotetrahydro-1H-imidazole-4-carboxylic acid C12H12N2O5 详情 详情
(VI) 15657 1-benzyl 5-(tert-butyl) (5S)-2-oxotetrahydro-1H-imidazole-1,5-dicarboxylate C16H20N2O5 详情 详情
(VII) 15658 1-benzyl 5-(tert-butyl) (5S)-3-methyl-2-oxotetrahydro-1H-imidazole-1,5-dicarboxylate C17H22N2O5 详情 详情
(VIII) 15659 tert-butyl (4S)-1-methyl-2-oxotetrahydro-1H-imidazole-4-carboxylate C9H16N2O3 详情 详情
(IX) 15660 tert-butyl (4S)-1-methyl-3-((2R)-2-[(4-methylphenyl)sulfonyl]propanoyl)-2-oxotetrahydro-1H-imidazole-4-carboxylate C19H26N2O7S 详情 详情
(X) 15661 ethyl (2S)-2-amino-4-phenylbutanoate C12H17NO2 详情 详情
(XI) 15662 tert-butyl (4S)-3-((2S)-2-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]propanoyl)-1-methyl-2-oxotetrahydro-1H-imidazole-4-carboxylate C24H35N3O6 详情 详情
(XII) 15663 ethyl (2S)-2-bromo-4-phenylbutanoate C12H15BrO2 详情 详情
(XIII) 10898 benzyl (2R)-2-aminopropanoate C10H13NO2 详情 详情
(XIV) 15665 ethyl (2S)-2-[[(1S)-2-(benzyloxy)-1-methyl-2-oxoethyl]amino]-4-phenylbutanoate C22H27NO4 详情 详情
(XV) 11360 (2S)-2-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]propionic acid; (S)-N-(1-Ethoxycarbonyl-3-phenylpropyl)-(S)-alanine 82717-96-2 C15H21NO4 详情 详情
(XVI) 15667 ethyl (2S)-2-([(1S)-2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-1-methyl-2-oxoethyl]amino)-4-phenylbutanoate C19H24N2O6 详情 详情

合成路线10

该中间体在本合成路线中的序号：(IX)

The reaction of the chiral epoxide (I) with isobutylamine (II) in refluxing ethanol gives the secondary amine (III), which is protected with benzyl chloroformate (IV) and TEA, yielding the dicarbamate (V). Selective deprotection of (V) with dry HCl in ethyl acetate affords the primary amine (VI), which is treated with 3(S)-tetrahydrofuryl N-succinimidinyl carbonate (VII) (prepared by condensation of tetrahydrofuran-3(S)-ol (VIII) with phosgene and N-hydroxysuccinimide (IX)) and DIEA in acetonitrile to provide the corresponding carbamate (X). The deprotection of (X) by hydrogenation with H2 over Pd/C in ethanol gives the secondary amine (XI), which is condensed with 4-nitrophenylsulfonyl chloride (XII) by means of NaHCO3 in dichloromethane/water to yield the sulfonamide (XIII). Finally, the nitro group of (XIII) is reduced with H2 over Pd/C in ethyl acetate to afford the target compound.

参考文献 中间体
合成目标
【1】 Tung, R.D.; Murcko, M.A.; Bhisetti, G.R. (Vertex Pharmaceuticals Inc.); Sulfonamide inhibitors of HIV-aspartyl protease. EP 0659181; EP 0885887; JP 1996501299; US 5585397; WO 9405639 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 19730 tert-butyl (1S)-1-[(2S)oxiranyl]-2-phenylethylcarbamate 98737-29-2 C15H21NO3 详情 详情
(II) 13306 2-Methyl-1-propanamine; Isobutylamine 78-81-9 C4H11N 详情 详情
(III) 44417 tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propylcarbamate 160232-08-6 C19H32N2O3 详情 详情
(IV) 10101 Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene 501-53-1 C8H7ClO2 详情 详情
(V) 44418 benzyl (2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl(isobutyl)carbamate C27H38N2O5 详情 详情
(VI) 44419 benzyl (2R,3S)-3-amino-2-hydroxy-4-phenylbutyl(isobutyl)carbamate C22H30N2O3 详情 详情
(VII) 39664 1-([[(3S)tetrahydro-3-furanyloxy]carbonyl]oxy)-2,5-pyrrolidinedione C9H11NO6 详情 详情
(VIII) 44420 (3S)-tetrahydro-3-furanol; (S)-3-Hydroxytetrahydrofuran 86087-23-2 C4H8O2 详情 详情
(IX) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(X) 44421 benzyl (2R,3S)-2-hydroxy-4-phenyl-3-([[(3S)tetrahydro-3-furanyloxy]carbonyl]amino)butyl(isobutyl)carbamate C27H36N2O6 详情 详情
(XI) 44422 (3S)tetrahydro-3-furanyl (1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propylcarbamate C19H30N2O4 详情 详情
(XII) 15809 4-nitrobenzenesulfonyl chloride 98-74-8 C6H4ClNO4S 详情 详情
(XIII) 44423 (3S)tetrahydro-3-furanyl (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[(4-nitrophenyl)sulfonyl]amino]propylcarbamate C25H33N3O8S 详情 详情

合成路线11

该中间体在本合成路线中的序号：(II)

The activation of N,N'-bis(benzyloxycarbonyl)-L-homocystine (I) with N-hydroxysuccinimide (II) by means of DCC gives the activated diester (III), which is condensed with N-(tert-butoxycarbonyl)-L-lysine (IV) by means of K2CO3, yielding the protected peptide (V). The selective deprotection of the epsilon amino groups of (V) by means of formic acid affords the dimeric peptide (VI), which is cleaved with dithiothreitol (DTT) to provide benzyloxycarbonyl-L-homocysteinyl-L-lysine (VII). The oxidation of (VII) with L-lysine epsilon aminotransferase (S. paucimobili or rec. E. coli) furnishes the formyl derivative (VIII), which is finally cyclized in acid medium to afford, through the nonisolated intermediate (IX), the target pyrido[2,1-b][1,3]thiazepine intermediate (X).

参考文献 中间体
合成目标
【1】 Patel, R.N.; Enzymatic synthesis of chiral intermediates for omapatrilat, an antihypertensive drug. Biomol Eng 2001, 17, 6, 167.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 50614 (2S)-2-[[(benzyloxy)carbonyl]amino]-4-[((3S)-3-[[(benzyloxy)carbonyl]amino]-3-carboxypropyl)disulfanyl]butyric acid C24H28N2O8S2 详情 详情
(II) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(III) 50618 benzyl (1S)-3-([(3S)-3-[[(benzyloxy)carbonyl]amino]-4-[(2,5-dioxo-1-pyrrolidinyl)oxy]-4-oxobutyl]disulfanyl)-1-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]propylcarbamate C32H34N4O12S2 详情 详情
(IV) 50619 N(epsilon)-Boc-L-lysine C11H22N2O4 详情 详情
(V) 50620 (10S,13S,20S,23S)-13,20-bis[[(benzyloxy)carbonyl]amino]-23-[4-[(tert-butoxycarbonyl)amino]butyl]-10-carboxy-2,2-dimethyl-4,12,21-trioxo-3-oxa-16,17-dithia-5,11,22-triazatetracosan-24-oic acid C46H68N6O14S2 详情 详情
(VI) 50621 (5S,12S,15S)-15-(4-aminobutyl)-5-([[(1S)-5-amino-1-carboxypentyl]amino]carbonyl)-12-[[(benzyloxy)carbonyl]amino]-3,13-dioxo-1-phenyl-2-oxa-8,9-dithia-4,14-diazahexadecan-16-oic acid C36H52N6O10S2 详情 详情
(VII) 50622 (2S)-6-amino-2-[((2S)-2-[[(benzyloxy)carbonyl]amino]-4-sulfanylbutanoyl)amino]hexanoic acid C18H27N3O5S 详情 详情
(VIII) 50623 (2S)-2-[((2S)-2-[[(benzyloxy)carbonyl]amino]-4-sulfanylbutanoyl)amino]-6-oxohexanoic acid C18H24N2O6S 详情 详情
(IX) 50624 (2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]-4-sulfanylbutanoyl)-6-hydroxy-2-piperidinecarboxylic acid C18H24N2O6S 详情 详情
(X) 50617 (4S,7S,10aS)-4-[[(benzyloxy)carbonyl]amino]-5-oxooctahydro-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid C18H22N2O5S 详情 详情

合成路线12

该中间体在本合成路线中的序号：(IV)

The condensation of L-valine (I) with 4-fluorobenzenesulfonyl chloride (II) by means of NaOH in THF/water gives N-(4-fluorobenzenesulfonyl)-L-valine (III), which is esterified with N-hydroxysuccinimide (IV) by means of EDC in dichloromethane to yield the activated ester (V). The condensation of (V) with L-leucinol (VI) by means of TEA in dichloromethane affords the N-(4-fluorobenzenesulfonyl)-L-valyl-L-leucinol (VII), which is finally oxidized with the SO3/Pyridine complex in DMSO/dichloromethane to provide the target leucinal derivative.

参考文献 中间体
合成目标
【1】 Fukiage, C.; et al.; SJA6017, a newly synthesized peptide aldehyde inhibitor of calpain: amelioration of cataract in cultured rat lenses. Biochim Biophys Acta 1997, 1361, 3, 304.
【2】 Fukiage, C.; Azuma, M.; Inoue, J.; Nakamura, M.; Yoshida, Y. (Senju Pharmaceuticals Co., Ltd.); Angiogenesis inhibitor. EP 0771565; EP 0927716; EP 0928786; JP 1998147564; JP 1998147566; JP 2001233847; US 6057290; US 6214800 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 37828 L-2-Amino-3-methylbutyric acid; L-2-Aminoisovaleric acid; 2-Aminoisovaleric acid; L-2-Amino-3-methylbutyric acid; L-alpha-Aminoisovaleric acid; L-valine; (S)-(+)-Valine; (S)-alpha-Aminoisovaleric acid 72-18-4 C5H11NO2 详情 详情
(II) 12292 4-Fluorobenzenesulfonyl chloride 349-88-2 C6H4ClFO2S 详情 详情
(III) 57911 (2S)-2-{[(4-fluorophenyl)sulfonyl]amino}-3-methylbutanoic acid C11H14FNO4S 详情 详情
(IV) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(V) 57912 N-((1S)-1-{[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}-2-methylpropyl)-4-fluorobenzenesulfonamide C15H17FN2O6S 详情 详情
(VI) 18171 L-(+)-leucinol; (S)-2-amino-4-methyl-1-pentanol; (2S)-2-amino-4-methyl-1-pentanol 7533-40-6 C6H15NO 详情 详情
(VII) 57913 (2S)-2-{[(4-fluorophenyl)sulfonyl]amino}-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-3-methylbutanamide C17H27FN2O4S 详情 详情

合成路线13

该中间体在本合成路线中的序号：(XI)

The intermediate epoxyamide (XVIII) has been obtained as follows: The cyclization of 2-methylacetoacetic acid ethyl ester (I) by means of potassium tert-butoxide gives 4-hydroxy-3-methyl-5,6-dihydro-2H-pyran-2-one (I), which is enantiomerically reduced with Mortierella isabellina ATCC 42613 yielding (S,S)-4-hydroxy-3-methyltetrahydropyran-2-one (III). The silylation of (III) by means of TBDMS-Cl, imidazole and DMAP affords the silyl ether (IV), which is reduced with DIBAL to the corresponding lactol and condensed with benzyldiphenylphosphine oxide (V) to give (3S,4R)-3-(tert-butyldimethylsilyloxy)-4-methyl-6-phenyl-5-hexen-1-ol (VI). The oxidation of (VI) with oxalyl chloride in dichloromethane/DMSO yields the corresponding aldehyde (VII), which is submitted to a Wittig condensation with trimethyl phosphonoacetate (VIII) by means of 1,1,3,3-tetramethylguanidine (TMG) to afford the octadienoic ester (IX). The hydrolysis of (IX) with KOH in dioxane gives the corresponding acid (X), which is esterified with N-hydroxysuccinimide (XI) and EDC to give the activated ester (XII). The epoxidation of (XII) with oxone or MCPBA, followed by HPLC chromatography separation of the resulting mixture of epoxides, gives the (2E,5S,6S,7R,8R)-5-(tert-butyldimethylsilyloxy)-7,8-epoxy-6-methyl-8-phenyl-2-octenoic acid N-succinimidinyl ester (XIII). The condensa-tion of activated ester (XIII) with amino acid (XIV) yields the corresponding amide (XV), which is desilylated with TBAF in DMF to afford the hydroxyacid (XVI). Finally, compound (XVI) is treated with DMSO and NaHCO3 and tert-butyl bromide to provide the desired intermediate the epoxyamide.

参考文献 中间体
合成目标
【1】 Zmijewski, M.J.J.; Zhang, T.Y.; Aikins, J.A.; Briggs, B.S. (Eli Lilly and Company; University of Hawaii; Wayne State University); Stereoselective process for producing antineoplastic agents. WO 0023429 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 10362 ethyl 2-methyl-3-oxobutanoate; ethyl 2-methylacetoacetate 609-14-3 C7H12O3 详情 详情
(II) 36494 4-hydroxy-3-methyl-5,6-dihydro-2H-pyran-2-one C6H8O3 详情 详情
(III) 36495 (3S,4S)-4-hydroxy-3-methyltetrahydro-2H-pyran-2-one C6H10O3 详情 详情
(IV) 36496 (3S,4S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3-methyltetrahydro-2H-pyran-2-one C12H24O3Si 详情 详情
(V) 36497 benzyl(diphenyl)phosphine oxide; benzyl(oxo)diphenylphosphorane 2959-74-2 C19H17OP 详情 详情
(VI) 36498 (3S,4R,5E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-6-phenyl-5-hexen-1-ol C19H32O2Si 详情 详情
(VII) 36499 (3S,4R,5E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-6-phenyl-5-hexenal C19H30O2Si 详情 详情
(VIII) 13272 Methyl 2-(dimethoxyphosphoryl)acetate; Trimethyl phosphoroacetate 5927-18-4 C5H11O5P 详情 详情
(IX) 34373 methyl (2E,5S,6R,7E)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-8-phenyl-2,7-octadienoate C22H34O3Si 详情 详情
(X) 34374 (2E,5S,6R,7E)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-8-phenyl-2,7-octadienoic acid C21H32O3Si 详情 详情
(XI) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(XII) 36500 1-[((2E,5S,6R,7E)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-8-phenyl-2,7-octadienoyl)oxy]-2,5-pyrrolidinedione C25H35NO5Si 详情 详情
(XIII) 36501 1-([(E,5S,6R)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-[(2R,3S)-3-phenyloxiranyl]-2-heptenoyl]oxy)-2,5-pyrrolidinedione C25H35NO6Si 详情 详情
(XIV) 36502 (2R)-2-amino-3-(3-chloro-4-methoxyphenyl)propionic acid C10H12ClNO3 详情 详情
(XV) 36503 (2R)-2-([(E,5S,6R)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-[(2R,3S)-3-phenyloxiranyl]-2-heptenoyl]amino)-3-(3-chloro-4-methoxyphenyl)propionic acid C31H42ClNO6Si 详情 详情
(XVI) 36504 N,N,N-tributyl-1-butanaminium (2R)-3-(3-chloro-4-methoxyphenyl)-2-([(E,5S,6S)-5-hydroxy-6-[(2R,3S)-3-phenyloxiranyl]-2-heptenoyl]amino)propanoate C41H63ClN2O6 详情 详情
(XVII) 36505 (methylsulfanyl)methyl (2R)-3-(3-chloro-4-methoxyphenyl)-2-([(E,5S,6S)-5-hydroxy-6-[(2R,3S)-3-phenyloxiranyl]-2-heptenoyl]amino)propanoate C27H32ClNO6S 详情 详情

合成路线14

该中间体在本合成路线中的序号：(XI)

The intermediate epoxyamide (XVII) has been obtained as follows: The cyclization of 2-methylacetoacetic acid ethyl ester (I) by means of potassium tert-butoxide gives 4-hydroxy-3-methyl-5,6-dihydro-2H-pyran-2-one (I), which is enantiomerically reduced with Mortierella isabellina ATCC 42613 yielding (S,S)-4-hydroxy-3-methyltetrahydropyran-2-one (III). The silylation of (III) by means of TBDMS-Cl, imidazole and DMAP affords the silyl ether (IV), which is reduced with DIBAL to the corresponding lactol and condensed with benzyldiphenylphosphine oxide (V) to give (3S,4R)-3-(tert-butyldimethylsilyloxy)-4-methyl-6-phenyl-5-hexen-1-ol (VI). The oxidation of (VI) with oxalyl chloride in dichloromethane/DMSO yields the corresponding aldehyde (VII), which is submitted to a Wittig condensation with trimethyl phosphonoacetate (VIII) by means of 1,1,3,3-tetramethylguanidine (TMG) to afford the octadienoic ester (IX). The hydrolysis of (IX) with KOH in dioxane gives the corresponding acid (X), which is esterified with N-hydroxysuccinimide (XI) and EDC to give the activated ester (XII). The epoxidation of (XII) with oxone or MCPBA, followed by HPLC chromatography separation of the resulting mixture of epoxides, gives the (2E,5S,6S,7R,8R)-5-(tert-butyldimethylsilyloxy)-7,8-epoxy-6-methyl-8-phenyl-2-octenoic acid N-succinimidinyl ester (XIII). The condensation of activated ester (XIII) with amino acid (XIV) yields the corresponding amide (XV), which is desilylated with TBAF in DMF to afford the hydroxyacid (XVI). Finally, compound (XVI) is treated with DMSO and NaHCO3 and tert-butyl bromide to provide the desired intermediate the epoxyamide (XVII).

参考文献 中间体
合成目标
【1】 Zmijewski, M.J.J.; Zhang, T.Y.; Aikins, J.A.; Briggs, B.S. (Eli Lilly and Company; University of Hawaii; Wayne State University); Stereoselective process for producing antineoplastic agents. WO 0023429 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 10362 ethyl 2-methyl-3-oxobutanoate; ethyl 2-methylacetoacetate 609-14-3 C7H12O3 详情 详情
(II) 36494 4-hydroxy-3-methyl-5,6-dihydro-2H-pyran-2-one C6H8O3 详情 详情
(III) 36495 (3S,4S)-4-hydroxy-3-methyltetrahydro-2H-pyran-2-one C6H10O3 详情 详情
(IV) 36496 (3S,4S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3-methyltetrahydro-2H-pyran-2-one C12H24O3Si 详情 详情
(V) 36497 benzyl(diphenyl)phosphine oxide; benzyl(oxo)diphenylphosphorane 2959-74-2 C19H17OP 详情 详情
(VI) 36498 (3S,4R,5E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-6-phenyl-5-hexen-1-ol C19H32O2Si 详情 详情
(VII) 36499 (3S,4R,5E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-6-phenyl-5-hexenal C19H30O2Si 详情 详情
(VIII) 13272 Methyl 2-(dimethoxyphosphoryl)acetate; Trimethyl phosphoroacetate 5927-18-4 C5H11O5P 详情 详情
(IX) 34373 methyl (2E,5S,6R,7E)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-8-phenyl-2,7-octadienoate C22H34O3Si 详情 详情
(X) 34374 (2E,5S,6R,7E)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-8-phenyl-2,7-octadienoic acid C21H32O3Si 详情 详情
(XI) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(XII) 36500 1-[((2E,5S,6R,7E)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-8-phenyl-2,7-octadienoyl)oxy]-2,5-pyrrolidinedione C25H35NO5Si 详情 详情
(XIII) 36501 1-([(E,5S,6R)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-[(2R,3S)-3-phenyloxiranyl]-2-heptenoyl]oxy)-2,5-pyrrolidinedione C25H35NO6Si 详情 详情
(XIV) 36502 (2R)-2-amino-3-(3-chloro-4-methoxyphenyl)propionic acid C10H12ClNO3 详情 详情
(XV) 36503 (2R)-2-([(E,5S,6R)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-[(2R,3S)-3-phenyloxiranyl]-2-heptenoyl]amino)-3-(3-chloro-4-methoxyphenyl)propionic acid C31H42ClNO6Si 详情 详情
(XVI) 36504 N,N,N-tributyl-1-butanaminium (2R)-3-(3-chloro-4-methoxyphenyl)-2-([(E,5S,6S)-5-hydroxy-6-[(2R,3S)-3-phenyloxiranyl]-2-heptenoyl]amino)propanoate C41H63ClN2O6 详情 详情
(XVII) 36505 (methylsulfanyl)methyl (2R)-3-(3-chloro-4-methoxyphenyl)-2-([(E,5S,6S)-5-hydroxy-6-[(2R,3S)-3-phenyloxiranyl]-2-heptenoyl]amino)propanoate C27H32ClNO6S 详情 详情

合成路线15

该中间体在本合成路线中的序号：(A)

Coupling of 4(S)-amino-4-carboxybutyric acid methyl ester (I) to acyl chloride (II) by means of Et3N in CH2Cl2 provides derivative (III), which is then converted into hydroxy derivative (IV) by means of N-hydroxysuccinimide (A) and DCC in THF followed by reduction with NaBH4 in H2O. Treatment of (IV) with ethoxymethylchloride (V) and DIEA in CH2Cl2 affords compound (VI), which is then methylated by means of lithium bis(trimethylsilyl)amide and methyl iodide in THF to give derivative (VII). Saponification of methyl ester (VII) by treatment with aqueous NaOH in THF affords carboxylic acid (VIII), which is then coupled to N-(1-methoxy-1,1-dimethyloxy)amine (IX) by means of HOBt and EDC in DMF and finally hydrolyzed with HCl in MeOH to furnish the target compound.

参考文献 中间体
合成目标
【1】 Sugiura, T.; Takahashi, K. (Ono Pharmaceutical Co., Ltd.); Aminobutanoic acid derivs.. EP 1024134; WO 9919296 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(I) 44795 (2S)-2-amino-5-methoxy-5-oxopentanoic acid 1499-55-4 C6H11NO4 详情 详情
(II) 44796 4-phenoxybenzoyl chloride C13H9ClO2 详情 详情
(III) 44797 (2S)-5-methoxy-5-oxo-2-[(4-phenoxybenzoyl)amino]pentanoic acid C19H19NO6 详情 详情
(IV) 44798 methyl (4S)-5-hydroxy-4-[(4-phenoxybenzoyl)amino]pentanoate C19H21NO5 详情 详情
(V) 13149 1-(Chloromethoxy)ethane; Chloromethyl ethyl ether 3188-13-4 C3H7ClO 详情 详情
(VI) 44799 methyl (4S)-5-(ethoxymethoxy)-4-[(4-phenoxybenzoyl)amino]pentanoate C22H27NO6 详情 详情
(VII) 44800 methyl (2S,4S)-5-(ethoxymethoxy)-2-methyl-4-[(4-phenoxybenzoyl)amino]pentanoate C23H29NO6 详情 详情
(VIII) 44801 (2S,4S)-5-(ethoxymethoxy)-2-methyl-4-[(4-phenoxybenzoyl)amino]pentanoic acid C22H27NO6 详情 详情
(IX) 44802 2-(aminooxy)-2-methoxypropane; O-(1-methoxy-1-methylethyl)hydroxylamine C4H11NO2 详情 详情

合成路线16

该中间体在本合成路线中的序号：(IX)

The reaction of the chiral epoxide (I) with isobutylamine (II) in refluxing ethanol gives the secondary amine (III), which is protected with benzyl chloroformate (IV) and TEA, yielding dicarbamate (V). Selective deprotection of (V) with dry HCl in ethyl acetate affords the primary amine (VI), which is treated with 3(S)-tetrahydrofuryl N-succinimidinyl carbonate (VII) -- obtained by reaction of tetrahydrofuran-3(S)-ol (VIII) first with phosgene and then with N-hydroxysuccinimide (IX) -- and DIEA in acetonitrile to provide the corresponding carbamate (X). Deprotection of (X) by hydrogenation with H2 over Pd/C in ethanol gives the secondary amine (XI), which is condensed with 4-nitrophenylsulfonyl chloride (XII) by means of NaHCO3 in dichloromethane/water to yield the sulfonamide intermediate (XIII).

参考文献 中间体
合成目标
【1】 Martin, L.; Castaner, R.M.; Sorbera, L.A.; Castaner, J.; Fosamprenavir. Drugs Fut 2001, 26, 3, 224.
【2】 Tung, R.D.; Murcko, M.A.; Bhisetti, G.R. (Vertex Pharmaceuticals Inc.); Sulfonamide inhibitors of HIV-aspartyl protease. EP 0659181; EP 0885887; JP 1996501299; US 5585397; WO 9405639 .
【3】 Tung, R.D. (Vertex Pharmaceuticals Inc.); THF-containing sulfonamide inhibitors of aspartyl protease. EP 0846110; WO 9633184 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 19730 tert-butyl (1S)-1-[(2S)oxiranyl]-2-phenylethylcarbamate 98737-29-2 C15H21NO3 详情 详情
(II) 13306 2-Methyl-1-propanamine; Isobutylamine 78-81-9 C4H11N 详情 详情
(III) 44417 tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propylcarbamate 160232-08-6 C19H32N2O3 详情 详情
(IV) 10101 Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene 501-53-1 C8H7ClO2 详情 详情
(V) 44418 benzyl (2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl(isobutyl)carbamate C27H38N2O5 详情 详情
(VI) 44419 benzyl (2R,3S)-3-amino-2-hydroxy-4-phenylbutyl(isobutyl)carbamate C22H30N2O3 详情 详情
(VII) 39664 1-([[(3S)tetrahydro-3-furanyloxy]carbonyl]oxy)-2,5-pyrrolidinedione C9H11NO6 详情 详情
(VIII) 44420 (3S)-tetrahydro-3-furanol; (S)-3-Hydroxytetrahydrofuran 86087-23-2 C4H8O2 详情 详情
(IX) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(X) 44421 benzyl (2R,3S)-2-hydroxy-4-phenyl-3-([[(3S)tetrahydro-3-furanyloxy]carbonyl]amino)butyl(isobutyl)carbamate C27H36N2O6 详情 详情
(XI) 44422 (3S)tetrahydro-3-furanyl (1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propylcarbamate C19H30N2O4 详情 详情
(XII) 15809 4-nitrobenzenesulfonyl chloride 98-74-8 C6H4ClNO4S 详情 详情
(XIII) 44423 (3S)tetrahydro-3-furanyl (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[(4-nitrophenyl)sulfonyl]amino]propylcarbamate C25H33N3O8S 详情 详情

合成路线17

该中间体在本合成路线中的序号：(XVI)

The reaction of the chiral epoxide (I) with isobutylamine (II) in refluxing ethanol gives the secondary amine (III), which is condensed with 4-nitrophenylsulfonyl chloride (XII) and TEA in hot toluene, yielding sulfonamide (XIV). Deprotection of (XIV) with HCl in hot toluene/water affords the primary amine (XV), which is condensed with imidazole-1-carboxylic acid 3(S)-tetrahydrofuryl ester (XVI) -- prepared by reaction of tetrahydrofuran-3(S)-ol (VIII) with carbonyldiimidazole (CDI) in ethyl acetate -- to provide intermediate (XIII).

参考文献 中间体
合成目标
【1】 Martin, L.; Castaner, R.M.; Sorbera, L.A.; Castaner, J.; Fosamprenavir. Drugs Fut 2001, 26, 3, 224.
【2】 Deininger, D.D.; O'Callaghan, J.; McGuie, S.; Singh, H.; Robertson, M.S.; Rodgers, K.; Tung, R.D.; Al-Farhan, E.; Rout, S.J. (Glaxo Group Ltd.); Process for the synthesis of HIV protease inhibitors. WO 9948885 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 19730 tert-butyl (1S)-1-[(2S)oxiranyl]-2-phenylethylcarbamate 98737-29-2 C15H21NO3 详情 详情
(II) 13306 2-Methyl-1-propanamine; Isobutylamine 78-81-9 C4H11N 详情 详情
(III) 44417 tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propylcarbamate 160232-08-6 C19H32N2O3 详情 详情
(VIII) 44420 (3S)-tetrahydro-3-furanol; (S)-3-Hydroxytetrahydrofuran 86087-23-2 C4H8O2 详情 详情
(XII) 15809 4-nitrobenzenesulfonyl chloride 98-74-8 C6H4ClNO4S 详情 详情
(XIII) 44423 (3S)tetrahydro-3-furanyl (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[(4-nitrophenyl)sulfonyl]amino]propylcarbamate C25H33N3O8S 详情 详情
(XIV) 44938 tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[(4-nitrophenyl)sulfonyl]amino]propylcarbamate C25H35N3O7S 详情 详情
(XV) 44939 N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-nitrobenzenesulfonamide 590-90-9 C20H27N3O5S 详情 详情
(XVI) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情

合成路线18

该中间体在本合成路线中的序号：(XXXV)

Metalation of 2-chloropyrazine (XVIII) with LTMP (prepared from BuLi and TMP) in THF, followed by formylation with DMF and subsequent reduction with NaBH4 yields (3-chloro-2-pyrazinyl)methanol (XXXI). Mitsunobu coupling of alcohol (XXXI) with phthalimide (XX) in the presence of PPh3 and DIAD in THF gives the N-substituted phthalimide (XXXII), which is then subjected to hydrazinolysis with NH2NH2 in CH2Cl2 to provide, after treatment with HCl, (3-chloro-2-pyrazinyl)methylamine dihydrochloride (XXXIII) . Coupling of amine (XXXIII) with succinimidyl ester (XXXIV) (prepared by condensation of 3-oxocyclobutanecarboxylic acid [XXXVI] with N-hydroxysuccinimide [XXXV] using DCC in isopropyl acetate [3]) in the presence of NaHCO3 in THF/H2O produces the 3-oxocyclobutanecarboxamide (XXXVII). Cyclization of amide (XXXVII) in the presence POCl3 and DMF in EtOAc affords 3-(8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone (XXXVIII), which is then brominated by means of NBS in DMF to yield the 1-bromo derivative (XXXIX) . Addition of CH3MgI to ketone (XXXIX) in THF, followed by chloride substitution with NH3, gives rise to cis-3-(8-amino-1-bromoimidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutanol (XII) .

参考文献 中间体
合成目标
【1】 Arnold, L.D., Cesario, C., Coate, H. et al. (OSI Pharmaceuticals, Inc.). 6,6-Bicyclic ring substituted heterobicyclic protein kinase inhibitors. EP 1740591, EP 2168968, EP 2305682, EP 2308879, JP 2007531754, JP 2009197013, US 200635031, WO 005097800.
【2】 Mulvihill, K.M., Castelhano, A.L. (OSI Pharmaceuticals, Inc.). Process to prepare substituted imidazopyrazine compounds. US 2007129547, WO 2007067709
【3】 Volk, B., Buck, E., Coate, H. et al. OSI-906: A novel, potent, and selective first-in-class small molecule insulin-like growth factor 1 receptor (IGF-1R) inhibitor in phase I clinical trials. 238th ACS Natl Meet (Aug 16-20, Washington) 2009, Abst MEDI 152.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XII) 68929 　 　 C11H13BrN4O 详情 详情
(XVIII) 24075 2-chloropyrazine 14508-49-7 C4H3ClN2 详情 详情
(XX) 12376 Phthalimide; 1H-Isoindole-1,3(2H)-dione; Isoindole-1,3-dione;Phthalic dicarboximide;Phenylimide;Isoindole-1,3-dione 85-41-6 C8H5NO2 详情 详情
(XXXI) 68943 (3-chloropyrazin-2-yl)methanol；3-chloro-Pyrazinemethanol；3-chloro-2-Pyrazinemethano 89283-32-9 C5H5ClN2O 详情 详情
(XXXII) 68944 2-((3-chloropyrazin-2-yl)methyl)isoindoline-1,3-dione 　 C13H8ClN3O2 详情 详情
(XXXIII) 68945 (3-chloropyrazin-2-yl)methanamine dihydrochloride 　 C5H6ClN3.2HCl 详情 详情
(XXXIV) 68946 2,5-dioxopyrrolidin-1-yl 3-oxocyclobutanecarboxylate 　 C9H9NO5 详情 详情
(XXXV) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
(XXXVI) 68947 3-oxocyclobutanecarboxylic acid；(3-Oxocyclobutyl)carboxylic acid 23761-23-1 C5H6O3 详情 详情
(XXXVII) 68948 N-((3-chloropyrazin-2-yl)methyl)-3-oxocyclobutanecarboxamide 　 C10H10ClN3O2 详情 详情
(XXXVIII) 68949 3-(8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone 　 C10H8ClN3O 详情 详情
(XXXIX) 68950 3-(1-bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone 　 C10H7BrClN3O 详情 详情

合成路线19

该中间体在本合成路线中的序号：(XIV)

Reaction of bromoacetyl bromide (I) with phenol at 80 °C gives the phenyl ester (II) , which by cyclization with (S)-(+)-phenylglycinol (III), previously treated with DIEA, in acetonitrile provides 5(S)-phenylmorpholin-2-one (IV) . Treatment of compound (IV) with HCl affords the corresponding HCl salt (V), which is reacted with NaHCO3 followed by coupling with benzodioxane-6-carboxaldehyde (VI) in refluxing EtOAc/toluene to yield the oxazine adduct (VII). Oxazine derivative (VII) can also be obtained by direct coupling of 5(S)-phenylmorpholin-2-one (IV) with aldehyde (VI) in refluxing toluene. Opening of adduct (VII) with pyrrolidine (VIII) in CH2Cl2, CHCl3 or refluxing THF followed by addition of HCl in refluxing MeOH leads to 3-(1,4-benzodioxan-6-yl)-3(R)-hydroxy-2(R)-(2-hydroxy-1-phenylethylamino)-1-(pyrrolidin-1-yl)propanone (IX), which is reduced with LiAlH4 in refluxing THF to give diol (X). Cleavage of diol (X) by means of H2 and Pd(OH)2 in the presence of either CF3COOH or HCl in MeOH or EtOH/H2O provides amine (XI), which is finally coupled with octanoic acid N-hydroxysuccinimide ester (XII) in CH2Cl2 . Ester (XII) is prepared by condensation of octanoyl chloride (XIII) with N-hydroxysuccinimide (XIV) by means of Et3N in CH2Cl2 .

参考文献 中间体
合成目标
【1】 Dellaria, J.F. Jr., Santarsiero, B.D. Enantioselective synthesis of alphaamino acid derivatives via the stereoselective alkylation of a homochiral glycine enolate synthon. J Org Chem 1989, 54(16): 3916-26.
【2】 Siegel, C., Hirth, B.H. (Genzyme Corp.). Synthesis of UDP-glucose:N-acylsphingosine glucosyltransferase inhibitors. CA 2453978, EP 1409467, EP 2067775, JP 2005255686, JP 2005502635, JP 2010095546, US 2003050299, US 6855830, WO 2003008399.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 14005 2-Bromoacetyl bromide; Bromoacetyl bromide 598-21-0 C2H2Br2O 详情 详情
(II) 69187 phenyl 2-bromoacetate;Phenyl bromoacetate;alpha-Phenyl Bromoacetate;Phenyl a-bromoacetate;bromoacetic acidphenyl ester 620-72-4 C8H7BrO2 详情 详情
(III) 10973 (2S)-2-Amino-2-phenyl-1-ethanol; (S)-2-Hydroxy-1-phenylethylamine; (S)-(+)-2-Phenylglycinol; (S)-2-Amino-2-phenyl-1-ethanol 20989-17-7 C8H11NO 详情 详情
(IV) 61798 (5S)-5-phenyl-2-morpholinone;5(S)-phenylmorpholin-2-one;(5S)-3,4,5,6-Tetrahydro-5-phenyl-4(H)-1,4-oxazin-2-one 144896-92-4 C10H11NO2 详情 详情
(V) 69188 5(S)-phenylmorpholin-2-one hydrochloride 　 C10H11NO2.HCl 详情 详情
(VI) 61797 2,3-dihydro-1,4-benzodioxine-6-carbaldehyde; 1,4-Benzodioxan-6-carboxaldehyde; 3,4-ethylenedioxybenzaldehyde ;benzodioxane-6-carboxaldehyde 29668-44-8 C9H8O3 详情 详情
(VII) 61799 (1S,3S,5S)-1,3-di(2,3-dihydro-1,4-benzodioxin-6-yl)-5-phenyltetrahydro-8H-[1,3]oxazolo[4,3-c][1,4]oxazin-8-one C28H25NO7 详情 详情
(VIII) 11376 Pyrrolidine 123-75-1 C4H9N 详情 详情
(IX) 61800 (2R,3R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-hydroxy-2-[(2-hydroxy-1-phenylethyl)amino]-1-(1-pyrrolidinyl)-1-propanone C23H28N2O5 详情 详情
(X) 61801 (1R,2R)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[(2-hydroxy-1-phenylethyl)amino]-3-(1-pyrrolidinyl)-1-propanol C23H30N2O4 详情 详情
(XI) 61802 (1R,2R)-2-amino-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-(1-pyrrolidinyl)-1-propanol C15H22N2O3 详情 详情
(XII) 69189 octanoic acid N-hydroxysuccinimide ester;2,5-Dioxopyrrolidin-1-yl octanoate;Caprylic acid N-hydroxysuccinimide ester;N-(Octanoyloxy)succinimide;N-Hydroxysuccinimidyl caprylate 14464-30-3 C12H19NO4 详情 详情
(XIII) 11123 Octanoyl chloride; n-Caprylyl chloride;Capryloyl chloride 111-64-8 C8H15ClO 详情 详情
(XIV) 10264 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione 6066-82-6 C4H5NO3 详情 详情
Extended Information