872728-82-0

Basic information

• Product Name: N-[4-(5-OXO-4,5-DIHYDRO-1,2,4-OXADIAZOL-3-YL)PHENYL]GLYCINE
• Synonyms: N-[4-(5-OXO-4,5-DIHYDRO-1,2,4-OXADIAZOL-3-YL)PHENYL]GLYCINE;N-[4-(2,5-Dihydro-5-oxo-1,2,4-oxadiazol-3-yl)phenyl]glycine;Glycine,N-[4-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)phenyl]-;2-((4-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)phenyl)amino)acetic acid;2-((4-(5-Oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)
• CAS NO: 872728-82-0
• Molecular Formula: C₁₀H₉N₃O₄
• Molecular Weight: 235.1962
• EINECS: 1312995-182-4
• Mol File: 872728-82-0.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 460.358 °C at 760 mmHg
• Flash Point: 232.217 °C
• Appearance: White solid
• Density: 1.57
• Storage Temp.: 2-8°C
• CAS DataBase Reference: N-[4-(5-OXO-4,5-DIHYDRO-1,2,4-OXADIAZOL-3-YL)PHENYL]GLYCINE(CAS DataBase Reference)
• NIST Chemistry Reference: N-[4-(5-OXO-4,5-DIHYDRO-1,2,4-OXADIAZOL-3-YL)PHENYL]GLYCINE(872728-82-0)
• EPA Substance Registry System: N-[4-(5-OXO-4,5-DIHYDRO-1,2,4-OXADIAZOL-3-YL)PHENYL]GLYCINE(872728-82-0)

Safety Data

• Hazardous Substances Data: 872728-82-0(Hazardous Substances Data)

Usage

General Description

N-[4-(5-OXO-4,5-DIHYDRO-1,2,4-OXADIAZOL-3-YL)PHENYL]GLYCINE is a chemical compound with the molecular formula C13H11N3O4. It is a derivative of oxadiazole and contains a glycine group. N-[4-(5-OXO-4,5-DIHYDRO-1,2,4-OXADIAZOL-3-YL)PHENYL]GLYCINE has potential applications in medicinal chemistry, particularly in the development of new drugs and pharmaceuticals. It may also have uses in research and chemical synthesis. Additional studies and experiments may be needed to fully understand the properties and potential uses of N-[4-(5-OXO-4,5-DIHYDRO-1,2,4-OXADIAZOL-3-YL)PHENYL]GLYCINE.

Synthetic route

2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylamino]acetic acid ethyl ester (872728-83-1) → 2-[4-(1,2,4-oxadiazol-5-one-3-yl)-phenylamino]-acetic acid (872728-82-0)

Conditions	Yield
Stage #1: 2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylamino]acetic acid ethyl ester With sodium hydroxide; water at 20 - 60℃; for 1h; pH=12.5; Stage #2: With hydrogenchloride at 0 - 60℃; pH=5;	98%
With sodium hydroxide; water at 20 - 60℃; pH=12.5; Product distribution / selectivity;	98%
Stage #1: 2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylamino]acetic acid ethyl ester With sodium hydroxide; water at 20 - 60℃; pH=12.5; Stage #2: With hydrogenchloride In water pH=3; Product distribution / selectivity;	98%
Stage #1: 2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylamino]acetic acid ethyl ester With sodium hydroxide; water at 20 - 60℃; for 1h; pH=12.5; Stage #2: With hydrogenchloride In water pH=3;	98%

2-[4-(1,2,4-oxadiazol-5-one-3-yl)-phenylamino]-acetic acid (872728-82-0) + ethyl 3-{[{2-amino-1-(methylamino)phen-4-yl}carbonyl](pyridyn-2-yl)amino}propanoate (212322-56-0) → 1-methyl-2-[N-[4-(1,2,4-oxadiazol-5-one-3-yl)phenyl]-amino-methyl]-benzimidazol-5-yl-carboxylic acid N-(2-pyridyl)-N-(2-ethoxycarbonylethyl)amide (872728-84-2)

Conditions	Yield
Stage #1: 2-[4-(1,2,4-oxadiazol-5-one-3-yl)-phenylamino]-acetic acid; ethyl 3-{[{2-amino-1-(methylamino)phen-4-yl}carbonyl](pyridyn-2-yl)amino}propanoate With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; ethyl acetate at 20℃; for 1.5h; Stage #2: With acetic acid at 90℃; Product distribution / selectivity;	85%
Stage #1: 2-[4-(1,2,4-oxadiazol-5-one-3-yl)-phenylamino]-acetic acid; ethyl 3-{[{2-amino-1-(methylamino)phen-4-yl}carbonyl](pyridyn-2-yl)amino}propanoate With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; ethyl acetate at 20℃; for 1.5h; Stage #2: With acetic acid at 90℃; Product distribution / selectivity;	85%
Stage #1: 2-[4-(1,2,4-oxadiazol-5-one-3-yl)-phenylamino]-acetic acid With pivaloyl chloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; 1-methyl-pyrrolidin-2-one at 0℃; for 0.5h; Stage #2: ethyl 3-{[{2-amino-1-(methylamino)phen-4-yl}carbonyl](pyridyn-2-yl)amino}propanoate With acetic acid In tetrahydrofuran; 1-methyl-pyrrolidin-2-one for 3h; Product distribution / selectivity; Heating / reflux;	76%

2-[4-(1,2,4-oxadiazol-5-one-3-yl)-phenylamino]-acetic acid (872728-82-0) + acetic acid (64-19-7) + ethyl 3-{[{2-amino-1-(methylamino)phen-4-yl}carbonyl](pyridyn-2-yl)amino}propanoate (212322-56-0) → 1-methyl-2-[N-[4-(1,2,4-oxadiazol-5-on-3-yl)phenyl]aminomethyl]benzimidazol-5-yl-carboxylic acid N-(2-pyridyl)-N-(2-ethoxycarbonylethyl)amide diacetate

Conditions	Yield
Stage #1: 2-[4-(1,2,4-oxadiazol-5-one-3-yl)-phenylamino]-acetic acid; ethyl 3-{[{2-amino-1-(methylamino)phen-4-yl}carbonyl](pyridyn-2-yl)amino}propanoate With 1,1'-carbonyldiimidazole In tetrahydrofuran at 50℃; for 19.5h; Stage #2: acetic acid In tetrahydrofuran for 1h; Heating / reflux;	75%

Upstream product

• 872728-83-1 2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylamino]acetic acid ethyl ester 

Downstream Products

• 872728-84-2 1-methyl-2-[N-[4-(1,2,4-oxadiazol-5-one-3-yl)phenyl]-amino-methyl]-benzimidazol-5-yl-carboxylic acid N-(2-pyridyl)-N-(2-ethoxycarbonylethyl)amide 

Relevant articles and documents

IMPROVED PROCESS FOR THE PREPARATION OF 4-(BENZIMIDAZOLYLMETHYLAMINO)-BENZAMIDES AND THE SALTS THEREOF

The invention relates to a process for preparing an optionally substituted 4-benzimidazol- 2-ylmethylamino)-benzamidine, characterised in that (a) an optionally correspondingly substituted diaminobenzene is condensed with 2 [4- (1,2,4-oxadiazol-5-on-3-yl)-phenylamino]-acetic acid, (b) i) the product thus obtained is hydrogenated and ii) optionally the amidino group is carbonylated, without isolating the intermediate product of the hydrogenation beforehand; as well as a process for preparing a salt of an optionally substituted 4(benzimidazol-2-ylmethylamino)-benzamidine, wherein (a) an optionally correspondingly substituted diaminobenzene is condensed with 2-[4-(1,2,4-oxadiazol-5-on-3-yl)-phenylamino]-acetic acid, (b) the product thus obtained is hydrogenated, and (c) i) optionally the amidino group is carbonylated and ii) without prior isolation of the intermediate product of the carbonylation the desired salt is isolated.

Process for the preparation of 4-(benzimidazolylmethylamino)-benzamidines

Production of optionally substituted 4-(benzimidazol-2-ylmethylamino)-benzamidines (I) involves: (a) condensing an optionally substituted diaminobenzene (II) with 2-(4-(1,2,4-oxadiazol-5-on-3-yl)-phenylamino)-acetic acid (III); (b) hydrogenating the product (IV); and (c) optionally carbonylating the amidino group. The intermediates (III), 2-(4-(1,2,4-oxadiazol-5-on-3-yl)-aniline (V) and benzimidazole derivatives (IV') are new compounds. Independent claims are included for the following new intermediates: 2-(4-(1,2,4-oxadiazol-5-on-3-yl)-phenylamino)-acetic acid of formula (III), 2-(4-(1,2,4-oxadiazol-5-on-3-yl)-phenylaminomethyl)-benzimidazoles of formula (IV') and 2-(4-(1,2,4-oxadiazol-5-on-3-yl)-aniline of formula (V). R 1> : alkyl or cycloalkyl; R 2> : alkyl (optionally substituted (os) by cycloalkyl-(1-3C) alkyl, where the 1-3C alkyl is os by COOH or a group convertible in vivo to COOH); or NR 21>R 22>; R 21> : alkyl (os by COOH, alkoxycarbonyl, COOCH 2Ph, CONHSO 2T, CONHSO 2Ph, 'trifluorosulfonylamino' (sic), trifluorosulfonylaminocarbonyl' (sic), or 1H-tetrazolyl); 2-4C alkyl substituted (but not on the alpha -C adjacent to the N) by OH, -O-T-Ph, -NH-T-COOH, -NH-T-COOT, -N(T)-T-COOH or -N(T)-T-COOT; or piperidinyl (os by T); R 22> : H; alkyl; cycloalkyl (os by T); 3-6C alkenyl or 3-6C alkynyl (both with the unsaturated part not bonded directly to N); phenyl (os by F, Cl, Br, T or OT); or benzyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, thienyl or imidazolyl (all os by T); or NR 21>R 22> : 5-7 membered cycloalkyleneimino (os by COOH or (1-4C) alkoxycarbonyl and optionally fused with a benzene ring); T : 1-3C alkyl; alkyl groups have 1-6C and cycloalkyl groups 3-7C unless specified otherwise. [Image] ACTIVITY : Anticoagulant. MECHANISM OF ACTION : Thrombin inhibitor.