WO2012028721A1 - Procédé d'amination réductrice d'acides α-céto-carboxyliques - Google Patents

Procédé d'amination réductrice d'acides α-céto-carboxyliques Download PDF

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Publication number
WO2012028721A1
WO2012028721A1 PCT/EP2011/065216 EP2011065216W WO2012028721A1 WO 2012028721 A1 WO2012028721 A1 WO 2012028721A1 EP 2011065216 W EP2011065216 W EP 2011065216W WO 2012028721 A1 WO2012028721 A1 WO 2012028721A1
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WO
WIPO (PCT)
Prior art keywords
process according
compound
hadgly
reductive amination
adgly
Prior art date
Application number
PCT/EP2011/065216
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English (en)
Inventor
Thorsten Wilhelm
Kerstin Knepper
Wolfgang Felzmann
David Benito-Garragori
Original Assignee
Sandoz Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
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Priority to EP11749456.7A priority Critical patent/EP2611770A1/fr
Publication of WO2012028721A1 publication Critical patent/WO2012028721A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/04—Formation of amino groups in compounds containing carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/04—Formation of amino groups in compounds containing carboxyl groups
    • C07C227/06—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
    • C07C227/08—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid by reaction of ammonia or amines with acids containing functional groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/56—Ring systems containing bridged rings
    • C07C2603/58—Ring systems containing bridged rings containing three rings
    • C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
    • C07C2603/74—Adamantanes

Definitions

  • the invention refers to a process for the reductive amination of a-keto carboxylic acids catalyzed by transition metal containing compounds.
  • Amines such as adamantyl glycine are key intermediates of therapeutic compounds, e. g. (3-hydroxyadamantan-l-yl)-glycine for dipeptityl peptidase IV inhibitors including Saxagliptin.
  • Saxagliptin (15',35',5 1 S -2-[(25)-2-amino-2-(3-hydroxy-l-adamantyl)acetyl]-2-azabicyclo [3.1.0]hexane-3-carbonitrile or its hydrochloride salt is an orally active reversible dipeptidyl peptidase-4 (DD4) inhibitor, which is a therapeutic agent for treatment of type-2 diabetes mellitus, obesity or related diseases, and is disclosed for example in US 6,395,767 B2, example 60.
  • DD4 dipeptidyl peptidase-4
  • Saxagliptin can be produced by coupling (S)-N-Boc-3-hydroxyadamant-l-yl glycine and methanoprolineamide as shown in the following scheme:
  • SAXA SAXA-HH Therefore 3-hydroxyadamant-l-yl glycine or a derivative thereof is a key intermediate for the synthesis of Saxagliptin.
  • a reductive amination of an a-oxo acetic acid substituted with an adamantyl rest is performed using an enzymatic enzyme, or transamination with a cell line.
  • an enzymatic enzyme or transamination with a cell line.
  • the aminolysis of an a-bromo-carboxylic acid followed by resolution is described.
  • WO2005106011 A2 amines are obtained by several steps including an enzymatic amination or transamination with a cell line.
  • keto carboxylic acids suffer from several disadvantages, e. g. expensive catalysts, use of high pressures of molecular hydrogen, separate addition of ammonia.
  • cycloalkyl as employed herein alone or as part of another group includes saturated cyclic hydrocarbon groups containing 1 to 3 rings, which includes monocyclic, bicyclic and tricyclic alkyls which includes bridge polycyclic alkyls containing in total 3 to 20 carbon atoms which includes cyclopropyl, cyclobutyl, cylcopentyl, cyclohexyl, adamantyl, norbornyl and 2,2,2-bicyclooctanyl.
  • substituents on the cycloalkyl group as employed herein can be halogens, alkyl, alkoxy, hydroxyl, aryl, aryloxy, arylalkyl, cycloalkyl, alkylhydroxy, alkylamido, alkylamino, oxo, acyl, amino, nitro, cyano, thiol, alkylthio, carboxycarbonyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkanoyl, formyl, sulfonyl and sulfinyl.
  • nitrogen source refers to ammonia and its derivatives - i.e. primary and secondary amines - and salts thereof.
  • hydrogenating reagent refers to all compounds and compound mixtures that are able to generate hydrogen under reaction conditions, e.g. molecular hydrogen, formate salts, phosphinic acid and its salts, alkylhydrosilanes and -siloxanes, 1 ,4-dihydropyridines and derivatives thereof (Hantz'sch esters) and related unsaturated heterocycles.
  • the present invention refers to a process for the preparation of a compound IV of the formula
  • A denotes a cycloalkyl substituent or substituted derivatives thereof, preferably adamantyl or substituted adamantyl, and the process comprises reacting of at least one compound of formula I with a hydrogenating reagent and a nitrogen source in the presence of a transition metal catalyst III.
  • the hydrogenating reagent is hydrogen and the nitrogen source is ammonia.
  • Hydrogen and ammonia are preferably generated in situ from a compound II.
  • the process according to the present invention is preferably performed in the absence of molecular hydrogen as cover gas and enzymes.
  • substituent A in compound I is adamantyl which is substituted or unsubstituted.
  • Compounds II generating ammonia and hydrogen is preferably a mixture of an ammonium salt and formate salt, more preferably ammonium formate.
  • the catalyst III is a mono- or polynuclear transition metal complex which may contain one or more mono- or polydentate, neutral or anionic ligands.
  • this transition metal catalyst contains palladium, rhodium or iridium.
  • the process according to the present invention is catalyzed homogeneously by a catalyst III, preferably with a rhodium (Rh) or an Iridium (Ir) containing catalyst.
  • a catalyst III preferably with a rhodium (Rh) or an Iridium (Ir) containing catalyst.
  • the catalysis is performed heterogeneously by a catalyst III, preferably with a palladium catalyst, particularly a palladium catalyst coated on a carrier like charcoal or insoluble inorganic materials.
  • a preferred carrier is charcoal.
  • ADGLY Adamantylglycinic acid
  • HADGLY 3-Hydroxyadamantylglycinic acid ADGA is well known in the art; with the described methodology it can be conveniently and selectively prepared by oxidizing ADMK with oxidants such as KMn0 4 in a suitable solvent such as water. This makes it a suitable starting material for the following steps.
  • HADGLY is produced in the following sequence of steps:
  • Preferred catalyst III for step 1 is a mono- or polynuclear transition metal complex which may contain one or more mono- or polydentate, neutral or anionic ligands.
  • this transition metal catalyst contains palladium, rhodium or iridium.
  • the process according to the present invention is catalyzed homogeneously by a catalyst III, preferably with a rhodium (Rh) or an Iridium (Ir) containing catalyst.
  • a catalyst III preferably with a rhodium (Rh) or an Iridium (Ir) containing catalyst.
  • the catalysis is performed heterogeneously by a catalyst III, preferably with a palladium catalyst, particularly a palladium catalyst coated on a carrier like charcoal or insoluble inorganic materials.
  • Preferred nitrogen source is ammonia or any of its derivatives - i.e. primary and secondary amines - or salts thereof.
  • Preferred hydrogenation reagent is molecular hydrogen or formate salts.
  • Preferred oxidants for step 2 are: sodium nitrite, nitric acid, oxygen, dioxirane, potassium permanganate, preferably HN0 3 .
  • the oxidation reaction is preferably performed in an acidic solvent such as TFA (trifluoracetic acid), methane sulfonic acid, triflic acid (trifluormethanesulfonic acid) or H 2 S0 4 , preferably H 2 S0 4 .
  • the oxidation is preferably performed at a temperature of -20°C to -40°C, preferably 0 °C to 25 °C.
  • HADGLY is directly obtained from HADGA by reductive amination using catalyst III, a nitrogen source and a hydrogenation reagent.
  • Preferred catalyst III is a mono- or polynuclear transition metal complex which may contain one or more mono- or polydentate, neutral or anionic ligands.
  • this transition metal catalyst contains palladium, rhodium or iridium.
  • the process according to the present invention is catalyzed homogeneously by a catalyst III, preferably with a rhodium (Rh) or an Iridium (Ir) containing catalyst.
  • a catalyst III preferably with a rhodium (Rh) or an Iridium (Ir) containing catalyst.
  • the catalysis is performed heterogeneously by a catalyst III, preferably with a palladium catalyst, particularly a palladium catalyst coated on a carrier like charcoal or insoluble inorganic materials.
  • Preferred nitrogen source is ammonia or any of its derivatives - i.e. primary and secondary amines - or salts thereof.
  • Preferred hydrogenation reagent is molecular hydrogen or formate salts.
  • HADGA may be obtained by oxidation of ADGA as described with reference to the oxidation of ADGLY to HADGLY.
  • ADGA Adamant- 1-yl glyoxylic acid
  • ADGLY Adamant- 1-yl glycine
  • HADGLY 3-Hydroxyadamant-l-yl glycine
  • Rh-catalyzed reductive amination Degassed MeOH (19.2 mL) was added under nitrogen atmosphere to a mixture of ADGA (1 Eq., 2.0 g, 9.6 mmol), ammonium formate (5 Eq., 3.0 g, 48 mmol) and [Cp*RhCl 2 ] 2 (0.25 mol%, 14.8 mg, 0.024 mmol) and the mixture was stirred at 55 °C for 18 h, whereupon the reaction mixture turned from orange to grey. The precipitated white solid was filtered off, washed with chilled MeOH and dried. Yield: 1.78 g (88 %).
  • ADGLY (450 mg, 2.15 mmol) was added portion wise to a cooled mixture of HN0 3 (65 %, 1.6 Eq., 0.24 mL, 3.44 mmol) and H 2 S0 4 (95 %, 37.3 Eq., 4.5 mL, 80.20 mmol) at 0 °C.
  • the reaction was stirred at room temperature for 4.5 h, after which the thick yellow solution was hydrolyzed with ice.
  • the pH of the solution was set to 5, and 50 mL MeOH were added.
  • the mixture was allowed to stand in the fridge overnight, after which the precipitated inorganic salts were filtered off.
  • Example 2 50.0 g HADGA (223 mmol, leq) were dissolved in 800 mL degassed methanol under nitrogen atmosphere in a 3 neck round bottom flask equipped with a reflux condenser, a mechanic stirrer and a thermometer. To the solution 70.3 g ammonium formate (1115 mmol, 5 eq) and 350 mg rhodium catalyst [RhCp*Cl 2 ] 2 (0.567 mmol, 0.25 mol%) was added under protecting atmosphere. The formed orange solution was stirred at 50 °C for 24 h. During the reaction time the color changed from orange to green/black and a suspension occurs.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Cette invention concerne un procédé d'amination réductrice d'acides α-céto-carboxyliques catalysé par des composés contenant un métal de transition.
PCT/EP2011/065216 2010-09-03 2011-09-02 Procédé d'amination réductrice d'acides α-céto-carboxyliques WO2012028721A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP11749456.7A EP2611770A1 (fr) 2010-09-03 2011-09-02 Procédé d'amination réductrice d'acides -céto-carboxyliques

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP10175258.2 2010-09-03
EP10175258 2010-09-03

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WO2012028721A1 true WO2012028721A1 (fr) 2012-03-08

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20120842A1 (it) * 2012-05-16 2013-11-17 Chemelectiva S R L Intermedi utili per la preparazione di saxagliptina e processo per la loro preparazione
CN104370769A (zh) * 2013-08-14 2015-02-25 重庆博腾制药科技股份有限公司 一种制备羟基金刚烷甘氨酸衍生物的方法
CN104892443A (zh) * 2015-04-07 2015-09-09 嘉兴学院 (s)-3-羟基金刚烷甘氨酸的制备方法
WO2016096905A1 (fr) * 2014-12-15 2016-06-23 Córdova Armando Synthèse d'amides et d'amines à partir d'aldéhydes ou de cétones par catalyse métallique hétérogène

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110041267A (zh) * 2019-05-29 2019-07-23 宁夏蓝丰精细化工有限公司 多菌灵清洁生产系统

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6395767B2 (en) 2000-03-10 2002-05-28 Bristol-Myers Squibb Company Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method
WO2003014061A1 (fr) 2001-08-09 2003-02-20 Degussa Ag Procede de production d'amines par amination de composes carbonyle dans des conditions d'hybridation par transfert
US20040048490A1 (en) 2002-09-09 2004-03-11 Asm Japan K.K. Interlayer insulation film used for multilayer interconnect of semiconductor integrated circuit and method of manufacturing the same
WO2004052850A2 (fr) 2002-12-09 2004-06-24 Bristol-Myers Squibb Company Procedes et composes pour produire des inhibiteurs de la dipeptidyle-peptidase et leurs intermediaires
WO2005106011A2 (fr) 2004-04-14 2005-11-10 Bristol-Myers Squibb Company Procede de preparation d'inhibiteurs de la dipeptidyl peptidase iv et de leurs intermediaires
WO2006128952A1 (fr) 2005-05-31 2006-12-07 Kemfine Oy Procede de preparation de derives d'adamantane

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6395767B2 (en) 2000-03-10 2002-05-28 Bristol-Myers Squibb Company Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method
EP1559710A2 (fr) 2000-03-10 2005-08-03 Bristol-Myers Squibb Company Inhibiteurs de la dipeptidyl-peptidase IV, à base de pyrrolidine, fusionnée à du cyclopropyle, procédé pour leur préparation et leur utilisation
WO2003014061A1 (fr) 2001-08-09 2003-02-20 Degussa Ag Procede de production d'amines par amination de composes carbonyle dans des conditions d'hybridation par transfert
US20040048490A1 (en) 2002-09-09 2004-03-11 Asm Japan K.K. Interlayer insulation film used for multilayer interconnect of semiconductor integrated circuit and method of manufacturing the same
WO2004052850A2 (fr) 2002-12-09 2004-06-24 Bristol-Myers Squibb Company Procedes et composes pour produire des inhibiteurs de la dipeptidyle-peptidase et leurs intermediaires
WO2005106011A2 (fr) 2004-04-14 2005-11-10 Bristol-Myers Squibb Company Procede de preparation d'inhibiteurs de la dipeptidyl peptidase iv et de leurs intermediaires
WO2006128952A1 (fr) 2005-05-31 2006-12-07 Kemfine Oy Procede de preparation de derives d'adamantane

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
DATABASE REAXYS [online] Elsevier Properties SA; KNOOP ET AL, XP002666942, Database accession no. Rx-ID: 757313 *
KITAMURA, M., LEE, D., HAYASHI, S., TANAKA, S., YOSHIMURA, M., J. ORG. CHEM., vol. 67, 2002, pages 8685
KNOOP ET AL., HOPPE-SEYELER'S ZEITSCHRIFT FÜR PHYSIOLOGISCHE CHEMIE, vol. 148, 1925, pages 311 *
KNOOP ET AL., HOPPE-SEYELER'S ZEITSCHRIFT FÜR PHYSIOLOGISCHE CHEMIE, vol. 170, 1927, pages 187 *
MASATO KITAMURA ET AL: "Catalytic Leuckart-Wallach-Type Reductive Amination of Ketones", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 67, no. 24, 1 November 2002 (2002-11-01), pages 8685 - 8687, XP055016172, ISSN: 0022-3263, DOI: 10.1021/jo0203701 *
NUGENT, T. C., EL-SHAZLY, M., ADV. SYNTH. CATAL., vol. 352, 2010, pages 753
SEIJI OGO ET AL: "pH-Dependent Chemoselective Synthesis of [alpha]-Amino Acids. Reductive Amination of [alpha]-Keto Acids with Ammonia Catalyzed by Acid-Stable Iridium Hydride Complexes in Water", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 126, no. 10, 1 March 2004 (2004-03-01), pages 3020 - 3021, XP055016225, ISSN: 0002-7863, DOI: 10.1021/ja031633r *
TARAROV, V. 1., KADYROV. R., RIERMEIER, T. H., B6MER, A., CHEM. COMMUN., 2000, pages 1867
TARAROV, V. L, B6MER, A., SYNLETT, 2005, pages 203
TRIPATHI, R. P., VERMA, S. S., PANDEY, J., TIWARE, V. K., CURR. ORG. CHEM., vol. 12, 2008, pages 1093

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20120842A1 (it) * 2012-05-16 2013-11-17 Chemelectiva S R L Intermedi utili per la preparazione di saxagliptina e processo per la loro preparazione
CN104370769A (zh) * 2013-08-14 2015-02-25 重庆博腾制药科技股份有限公司 一种制备羟基金刚烷甘氨酸衍生物的方法
CN104370769B (zh) * 2013-08-14 2017-05-31 重庆博腾制药科技股份有限公司 一种制备羟基金刚烷甘氨酸衍生物的方法
WO2016096905A1 (fr) * 2014-12-15 2016-06-23 Córdova Armando Synthèse d'amides et d'amines à partir d'aldéhydes ou de cétones par catalyse métallique hétérogène
CN107001312A (zh) * 2014-12-15 2017-08-01 有机燃料瑞典公司 通过非均相金属催化由醛或酮合成酰胺和胺
US10308588B2 (en) 2014-12-15 2019-06-04 Organofuel Sweden Ab Synthesis of amides and amines from aldehydes or ketones by heterogeneous metal catalysis
CN104892443A (zh) * 2015-04-07 2015-09-09 嘉兴学院 (s)-3-羟基金刚烷甘氨酸的制备方法
CN104892443B (zh) * 2015-04-07 2016-08-24 嘉兴学院 (s)-3-羟基金刚烷甘氨酸的制备方法

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