CAS: 823817-55-6; Sitagliptin Ep Impurity A

该化合物是一种复杂的有机化合物,其特性是其独特的三硝酸和环形结构,有助于其潜在的生物活动.三氟甲基组的存在会加强其亲脂性,并可能影响其与生物目标的相互作用.这种化合物具有氨酸衍生物特征,表明其在医药化学,特别是药物设计中的潜在应用.氨酸混合物的立体化学学表明与生物受体的具体相互作用,这对于其药理特性至关重要.此外,该化合物的结构复杂性可能会导致有趣的物理化学特性,例如溶性与稳定性,这对于其在治疗应用中的效力至关重要.

结构式图片

物理性质

MSDS等安全信息

上下游产品

(R)-tert-butyl 4-oxo-4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-ylcarbamate 2,4,5-trifluorobenzyl bromide 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid(2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (-)dibenzolyl-L-tartaric acid salt (2S)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (-)dibenzolyl-L-tartaric acid salt dibenzoyl-D-tartaric acid (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine dibenzoyl-D-tartaric acid (2S)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine

合成工艺路线路线简述

  • 1883657-40-6 = 823817-55-6
    反应条件:1.1 Reagents: Lithium Hydroxide Solvents: Tetrahydrofuran,Water; Rt1.2 Reagents: Hydrochloric Acid Solvents: Water; Ph 52.1 -
    标题:Chiral Lewis Base-Catalyzed,Enantioselective Reduction Of Unprotected β-Enamino Esters With Trichlorosilane
    作者:Ye,Jianheng; Et Al
    参考文献:Advanced Synthesis & Catalysis 日期:2016 卷标:358(7) 页码:1042-1047]

    764667-65-4 + 2627-86-3 = 823817-55-6
    反应条件:1.1 Reagents: Acetic Acid Solvents: Toluene; Rt -> 110 °C; 2 - 3 H,110 °C; 110 °C -> 30 °C1.2 Reagents: Methanesulfonic Acid,Sodium Borohydride Solvents: Toluene,1,2-Dimethoxyethane; -65 °C; 1 - 1.5 H,-65 °C; -65 °C -> -90 °C1.3 Solvents: Isopropanol; < -90 °C; 2.5 - 3 H,-90 °C1.4 Solvents: Water; -90 °C -> 35 °C; 2.5 - 3 H,25 - 35 °C1.5 Reagents: Ammonia Solvents: Water1.6 Reagents: Hydrochloric Acid Solvents: Isopropanol; 30 °C; 0.5 H,30 °C2.1 Reagents: Hydrogen Catalysts: Palladium Solvents: Isopropanol,Water; Rt -> 70 °C; 8 - 10 H,105 Psi,65 - 70 °C; 70 °C -> 30 °C2.2 Reagents: Acetic Acid; 1 H,80 - 85 °C; 85 °C -> 30 °C; 2 H,25 - 30 °C
    标题:Efficient And Convenient Synthetic Routes For Sitagliptin Impurities
    作者:Metil,Dattatray S.; Et Al
    参考文献:Chemistryselect 日期:2018 卷标:3(10) 页码:2723-2729]

    = 823817-55-6
    反应条件:1.1 Reagents: Acetic Acid,Potassium Borohydride Solvents: Dichloromethane; -30 - 35 °C; 30 Min,35 °C1.2 Solvents: Dichloromethane; 2 H,Rt1.3 Reagents: Sodium Hydroxide,Hydrochloric Acid Solvents: Water; Ph 8,Rt2.1 Reagents: Formic Acid,Hydrogen Catalysts: Palladium Dihydroxide Solvents: Isopropanol,Water; Rt -> 50 °C2.2 Reagents: Sodium Hydroxide Solvents: Water; Ph 8,Rt
    标题:Synthesis Of Related Substance Of Sitagliptin Phosphate
    作者:Wu,Zonghao; Et Al
    参考文献:Shandong Huagong 日期:2017 卷标:46(14) 页码:19-21]

    1526941-29-6 = 823817-55-6
    反应条件:1.1 Reagents: Periodic Acid (H5Io6) Catalysts: Chromium Trioxide Solvents: Acetonitrile; 0 °C; 1 H,0 °C1.2 Reagents: Disodium Phosphate Solvents: Water2.1 Reagents: 1-Ethyl-3-(3′-Dimethylaminopropyl)Carbodiimide,1-Hydroxybenzotriazole,Diisopropylethylamine Solvents: Dimethylformamide; 2 D,23 °C3.1 Reagents: Methanesulfonic Acid,Trifluoroacetic Acid Solvents: Thioanisole; 12 H,40 °C
    标题:Catalytic Enantioselective Allylic Amination Of Olefins For The Synthesis Of Ent-Sitagliptin
    作者:Bao,Hongli; Et Al
    参考文献:Synlett 日期:2013 卷标:24(18) 页码:2459-2463]

    24424-99-5 + 1883657-39-3 = 823817-55-6
    反应条件:1.1 Reagents: Triethylamine Solvents: Dichloromethane; Rt2.1 Reagents: Lithium Hydroxide Solvents: Tetrahydrofuran,Water; Rt2.2 Reagents: Hydrochloric Acid Solvents: Water; Ph 53.1 -
    标题:Chiral Lewis Base-Catalyzed,Enantioselective Reduction Of Unprotected β-Enamino Esters With Trichlorosilane
    作者:Ye,Jianheng; Et Al
    参考文献:Advanced Synthesis & Catalysis 日期:2016 卷标:358(7) 页码:1042-1047]

    764667-65-4 + 3886-69-9 = 823817-55-6
    反应条件:1.1 Reagents: Acetic Acid Solvents: Isopropanol; Rt; Rt -> 45 °C; 12 H,45 °C2.1 Reagents: Acetic Acid,Potassium Borohydride Solvents: Dichloromethane; -30 - 35 °C; 30 Min,35 °C2.2 Solvents: Dichloromethane; 2 H,Rt2.3 Reagents: Sodium Hydroxide,Hydrochloric Acid Solvents: Water; Ph 8,Rt3.1 Reagents: Formic Acid,Hydrogen Catalysts: Palladium Dihydroxide Solvents: Isopropanol,Water; Rt -> 50 °C3.2 Reagents: Sodium Hydroxide Solvents: Water; Ph 8,Rt
    标题:Synthesis Of Related Substance Of Sitagliptin Phosphate
    作者:Wu,Zonghao; Et Al
    参考文献:Shandong Huagong 日期:2017 卷标:46(14) 页码:19-21]

    1883657-38-2 = 823817-55-6
    反应条件:1.1 Reagents: Water,Trichlorosilane Catalysts: (2S)-1-Formyl-N-[(1S,2R)-2-(Methoxymethoxy)-1,2-Diphenylethyl]-2-Piperidinecarbo... Solvents: Dichloromethane; 0 °C; 36 H,0 °C1.2 Reagents: Sodium Bicarbonate Solvents: Water2.1 Reagents: Triethylamine Solvents: Dichloromethane; Rt3.1 Reagents: Lithium Hydroxide Solvents: Tetrahydrofuran,Water; Rt3.2 Reagents: Hydrochloric Acid Solvents: Water; Ph 54.1 -
    标题:Chiral Lewis Base-Catalyzed,Enantioselective Reduction Of Unprotected β-Enamino Esters With Trichlorosilane
    作者:Ye,Jianheng; Et Al
    参考文献:Advanced Synthesis & Catalysis 日期:2016 卷标:358(7) 页码:1042-1047]

    922178-94-7 = 823817-55-6 [标题:Reaction Conditions
    标题:Chiral Lewis Base-Catalyzed,Enantioselective Reduction Of Unprotected β-Enamino Esters With Trichlorosilane
    作者:Ye,Jianheng; Et Al
    参考文献:Advanced Synthesis & Catalysis 日期:2016 卷标:358(7) 页码:1042-1047]

    = 823817-55-6
    反应条件:1.1 Reagents: Hydrogen Catalysts: Palladium Solvents: Isopropanol,Water; Rt -> 70 °C; 8 - 10 H,105 Psi,65 - 70 °C; 70 °C -> 30 °C1.2 Reagents: Acetic Acid; 1 H,80 - 85 °C; 85 °C -> 30 °C; 2 H,25 - 30 °C
    标题:Efficient And Convenient Synthetic Routes For Sitagliptin Impurities
    作者:Metil,Dattatray S.; Et Al
    参考文献:Chemistryselect 日期:2018 卷标:3(10) 页码:2723-2729]

    = 823817-55-6
    反应条件:1.1 Reagents: Methanesulfonic Acid,Trifluoroacetic Acid Solvents: Thioanisole; 12 H,40 °C
    标题:Catalytic Enantioselective Allylic Amination Of Olefins For The Synthesis Of Ent-Sitagliptin
    作者:Bao,Hongli; Et Al
    参考文献:Synlett 日期:2013 卷标:24(18) 页码:2459-2463]

    1683551-57-6 = 823817-55-6
    反应条件:1.1 Reagents: Formic Acid,Hydrogen Catalysts: Palladium Dihydroxide Solvents: Isopropanol,Water; Rt -> 50 °C1.2 Reagents: Sodium Hydroxide Solvents: Water; Ph 8,Rt
    标题:Synthesis Of Related Substance Of Sitagliptin Phosphate
    作者:Wu,Zonghao; Et Al
    参考文献:Shandong Huagong 日期:2017 卷标:46(14) 页码:19-21]

    762240-92-6 = 823817-55-6
    反应条件:1.1 Reagents: 1-Ethyl-3-(3′-Dimethylaminopropyl)Carbodiimide,1-Hydroxybenzotriazole,Diisopropylethylamine Solvents: Dimethylformamide; 2 D,23 °C2.1 Reagents: Methanesulfonic Acid,Trifluoroacetic Acid Solvents: Thioanisole; 12 H,40 °C
    标题:Catalytic Enantioselective Allylic Amination Of Olefins For The Synthesis Of Ent-Sitagliptin
    作者:Bao,Hongli; Et Al
    参考文献:Synlett 日期:2013 卷标:24(18) 页码:2459-2463]

    = 823817-55-6
    反应条件:1.1 Reagents: 9-Borabicyclo[3.3.1]Nonane Solvents: Tetrahydrofuran; 1 H,23 °C; 23 °C -> 0 °C1.2 Reagents: Sodium Hydroxide,Hydrogen Peroxide Solvents: Water; 0 °C2.1 Reagents: Periodic Acid (H5Io6) Catalysts: Chromium Trioxide Solvents: Acetonitrile; 0 °C; 1 H,0 °C2.2 Reagents: Disodium Phosphate Solvents: Water3.1 Reagents: 1-Ethyl-3-(3′-Dimethylaminopropyl)Carbodiimide,1-Hydroxybenzotriazole,Diisopropylethylamine Solvents: Dimethylformamide; 2 D,23 °C4.1 Reagents: Methanesulfonic Acid,Trifluoroacetic Acid Solvents: Thioanisole; 12 H,40 °C
    标题:Catalytic Enantioselective Allylic Amination Of Olefins For The Synthesis Of Ent-Sitagliptin
    作者:Bao,Hongli; Et Al
    参考文献:Synlett 日期:2013 卷标:24(18) 页码:2459-2463]

    = 823817-55-6
    反应条件:1.1 Catalysts: Palladium Trifluoroacetate,2,2′-Methylenebis[(4S)-4-Tert-Butyl-2-Oxazoline] Solvents: 1,2-Dichloroethane; Rt -> -20 °C; 30 Min,50 °C; 7 D,-15 °C1.2 Reagents: Potassium Carbonate Solvents: Methanol,Water; 14 H,23 °C2.1 Reagents: 9-Borabicyclo[3.3.1]Nonane Solvents: Tetrahydrofuran; 1 H,23 °C; 23 °C -> 0 °C2.2 Reagents: Sodium Hydroxide,Hydrogen Peroxide Solvents: Water; 0 °C3.1 Reagents: Periodic Acid (H5Io6) Catalysts: Chromium Trioxide Solvents: Acetonitrile; 0 °C; 1 H,0 °C3.2 Reagents: Disodium Phosphate Solvents: Water4.1 Reagents: 1-Ethyl-3-(3′-Dimethylaminopropyl)Carbodiimide,1-Hydroxybenzotriazole,Diisopropylethylamine Solvents: Dimethylformamide; 2 D,23 °C5.1 Reagents: Methanesulfonic Acid,Trifluoroacetic Acid Solvents: Thioanisole; 12 H,40 °C
    标题:Catalytic Enantioselective Allylic Amination Of Olefins For The Synthesis Of Ent-Sitagliptin
    作者:Bao,Hongli; Et Al
    参考文献:Synlett 日期:2013 卷标:24(18) 页码:2459-2463]

    = 823817-55-6
    反应条件:1.1 Reagents: Potassium Carbonate Solvents: Methanol,Water; Rt -> -20 °C; 30 Min,50 °C; 7 D,-15 °C2.1 Reagents: 9-Borabicyclo[3.3.1]Nonane Solvents: Tetrahydrofuran; 1 H,23 °C; 23 °C -> 0 °C2.2 Reagents: Sodium Hydroxide,Hydrogen Peroxide Solvents: Water; 0 °C3.1 Reagents: Periodic Acid (H5Io6) Catalysts: Chromium Trioxide Solvents: Acetonitrile; 0 °C; 1 H,0 °C3.2 Reagents: Disodium Phosphate Solvents: Water4.1 Reagents: 1-Ethyl-3-(3′-Dimethylaminopropyl)Carbodiimide,1-Hydroxybenzotriazole,Diisopropylethylamine Solvents: Dimethylformamide; 2 D,23 °C5.1 Reagents: Methanesulfonic Acid,Trifluoroacetic Acid Solvents: Thioanisole; 12 H,40 °C
    标题:Catalytic Enantioselective Allylic Amination Of Olefins For The Synthesis Of Ent-Sitagliptin
    作者:Bao,Hongli; Et Al
    参考文献:Synlett 日期:2013 卷标:24(18) 页码:2459-2463]

    2033-24-1 + 209995-38-0 = 823817-55-6
    反应条件:1.1 Reagents: Dicyclohexylcarbodiimide,4-(Dimethylamino)Pyridine Solvents: Dichloromethane; 16 H,0 °C1.2 Solvents: Isopropanol; 4 H,Reflux1.3 Reagents: Ammonium Acetate Solvents: Toluene; 6 H,Reflux2.1 Reagents: Water,Trichlorosilane Catalysts: (2S)-1-Formyl-N-[(1S,2R)-2-(Methoxymethoxy)-1,2-Diphenylethyl]-2-Piperidinecarbo... Solvents: Dichloromethane; 0 °C; 36 H,0 °C2.2 Reagents: Sodium Bicarbonate Solvents: Water3.1 Reagents: Triethylamine Solvents: Dichloromethane; Rt4.1 Reagents: Lithium Hydroxide Solvents: Tetrahydrofuran,Water; Rt4.2 Reagents: Hydrochloric Acid Solvents: Water; Ph 55.1 -
    标题:Chiral Lewis Base-Catalyzed,Enantioselective Reduction Of Unprotected β-Enamino Esters With Trichlorosilane
    作者:Ye,Jianheng; Et Al
    参考文献:Advanced Synthesis & Catalysis 日期:2016 卷标:358(7) 页码:1042-1047]

    667-20-9 = 823817-55-6
    反应条件:1.1 Solvents: Diethyl Ether; Rt -> 0 °C; 12 H,4 °C2.1 Catalysts: Palladium Trifluoroacetate,2,2′-Methylenebis[(4S)-4-Tert-Butyl-2-Oxazoline] Solvents: 1,2-Dichloroethane; Rt -> -20 °C; 30 Min,50 °C; 7 D,-15 °C2.2 Reagents: Potassium Carbonate Solvents: Methanol,Water; 14 H,23 °C3.1 Reagents: 9-Borabicyclo[3.3.1]Nonane Solvents: Tetrahydrofuran; 1 H,23 °C; 23 °C -> 0 °C3.2 Reagents: Sodium Hydroxide,Hydrogen Peroxide Solvents: Water; 0 °C4.1 Reagents: Periodic Acid (H5Io6) Catalysts: Chromium Trioxide Solvents: Acetonitrile; 0 °C; 1 H,0 °C4.2 Reagents: Disodium Phosphate Solvents: Water5.1 Reagents: 1-Ethyl-3-(3′-Dimethylaminopropyl)Carbodiimide,1-Hydroxybenzotriazole,Diisopropylethylamine Solvents: Dimethylformamide; 2 D,23 °C6.1 Reagents: Methanesulfonic Acid,Trifluoroacetic Acid Solvents: Thioanisole; 12 H,40 °C
    标题:Catalytic Enantioselective Allylic Amination Of Olefins For The Synthesis Of Ent-Sitagliptin
    作者:Bao,Hongli; Et Al
    参考文献:Synlett 日期:2013 卷标:24(18) 页码:2459-2463
📜(2Z)-4-氧代-4-[3-(三氟甲基)-5,6-二氢-[1,2,4]三唑并[4,3-A]吡嗪-7-(8H)-基]-1-(2,4,5-三氟苯基)丁-2-酮置于甲酸,10 Wt% Pd(Oh)2 On Carbon,三乙酰氧基硼氢化钠,三氟乙酸体系中,用 四氢呋喃,甲醇,1,2-二氯乙烷 作为反应溶剂,化学反应 12.5H,反应生成 西他列汀杂质1
参考文献:一种西他列汀及其中间体的制备方法
标题:一种西他列汀及其中间体的制备方法
摘要:本发明涉及药物合成领域,特别涉及一种西他列汀及其中间体的制备方法.式iii所示化合物的制备方法为在第一有机溶剂存在的条件下,取式i所示化合物和式ii所示化合物,在还原剂和有机酸的作用下发生还原胺化反应,得到式iii所示化合物;还原剂选自氰基硼氢化钠或三乙酰氧基硼氢化钠.本发明提供的制备方法无需使用贵重金属作为催化剂,降低了成本,简化了合成过程,提高了收率,使西他列汀的化学纯度和光学纯度均得到了提高;其中,R为甲基或氨甲酰基;ar为苯基,单取代苯基或多取代苯基.

海关参考信息

专利信息


专利号:US-8476437-B2
优先权日:2008-08-27
标题:Process for preparation of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro [1,2,4]-triazolo[4,3-a]pyrazin-7(8H)-yl]-l-(2,4,5-trifluorophenyl)butan-2-amine and new impurities in preparation thereof
发明人：KOTHARI HIMANSHU MADHUSUDAN; DAVE MAYANK GHANSHYAMBHAI; PANDEY BIPIN; SHUKLA BHAVIN SHRIPRASAD
权利人:KOTHARI HIMANSHU MADHUSUDAN; DAVE MAYANK GHANSHYAMBHAI; PANDEY BIPIN; SHUKLA BHAVIN SHRIPRASAD; CADILA HEALTHCARE LTD
摘要:The present invention relates to synthesis of β-amino acid derivatives of formula (I) and its salts of formula (Ia) by a novel process. The process comprises the reduction of a protected or unprotected prochiral β-amino acrylic acid or derivative there of, by using borane containing reducing agents at atmospheric pressure. The resulting racemic β-amino compound is resolved to a pure stereoisomer of formula (I), specifically to (2R)-4-oxo-4-[3-Ctrifluoromethyl)-5,6-dihydrol[1,2,4]triazolo[4,3-alpyrazin-7(8H)-yl]-1-(2,4,4-trifluorophenyl)butan-2-amine. In an embodiment the invention disclosed polymorphic forms of formula (I), phosphate salt of formula (I) and also a Dibenzoyl-L-tartaric acid salt of formula (I).

专利号:JP-6199556-B2
优先权日:2009-05-11
标题:Synthesis of sitagliptin

专利号:JP-2016029051-A
优先权日:2009-05-11
标题 :Synthesis of sitagliptin

专利号:CN-102574856-A
优先权日:2009-05-11
标题 :Synthesis of sitagliptin

专利号:CN-102574856-B
优先权日:2009-05-11
标 题:The synthesis of sitagliptin

专利号:JP-2012526791-A
优先权日:2009-05-11
标 题 :Synthesis of sitagliptin

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合成参考文献


参考文献:10.1055/s-0033-1340079
摘要:Bao H, Bayeh L, Tambar UK. Catalytic Enantioselective Allylic Amination of Olefins for the Synthesis of ent-Sitagliptin. Synlett. 2013 Nov 01;24(18):2459–63.
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