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CAS No. : | 540-69-2 | MDL No. : | MFCD00013103 |
Formula : | CH5NO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | VZTDIZULWFCMLS-UHFFFAOYSA-N |
M.W : | 63.06 | Pubchem ID : | 2723923 |
Synonyms : |
Ammonium formate
|
Num. heavy atoms : | 4 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 13.12 |
TPSA : | 40.13 Ų |
GI absorption : | Low |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -8.96 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | -3.21 |
Log Po/w (WLOGP) : | -1.26 |
Log Po/w (MLOGP) : | -5.69 |
Log Po/w (SILICOS-IT) : | -0.23 |
Consensus Log Po/w : | -2.08 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 3.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | 1.79 |
Solubility : | 3900.0 mg/ml ; 61.9 mol/l |
Class : | Highly soluble |
Log S (Ali) : | 2.94 |
Solubility : | 54600.0 mg/ml ; 865.0 mol/l |
Class : | Highly soluble |
Log S (SILICOS-IT) : | 0.97 |
Solubility : | 593.0 mg/ml ; 9.4 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.0 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P264-P270-P301+P312-P330-P501 | UN#: | N/A |
Hazard Statements: | H302 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | at 190℃; for 3.5 h; | Im trockenen Doppelmantel-Glasreaktor wurden 272 g ( 6.0 mol) Formamid vorgelegt und bei guter Rhrung auf 190 C (Sumpftemperatur) erhitzt. Innerhalb von 3 h wurden dann 209 g (1,5 mol) 95percentiges 4,4-Dimethoxy-2-butanon mit Hilfe einer Schlauchpumpe kontinuierlich zudosiert. Gleichzeitig wurden ber Kopf ber ein einfaches, ummanteltes Steigrohr und einen absteigenden, auf 50 C temperierten Khler, 342 g eines gelben Reaktionsdestillates abgenommen, das aus Methanol, Wasser, 4-Methylpyrimidin und Ammoniumformiat bestand. Die Kopftemperatur fiel fast unmittelbar nach Ende der Dosierung von ca. 158 C deutlich ab. Anschlieend lie man noch 30 min nachreagieren. Das bei der Reaktion als Nebenprodukt gebildete Ammoniumformiat (ca. 15 g) neigt dazu, sich im Gasraum niederzuschlagen bzw. auf der Khlseite bei zu starker Khlung auszufallen. Bei der genannten 4,4-Dimethoxy-2-butanon-Dosierrate splte der Destillatstrom das Salz in die Vorlage. Die lbadtemperaturen lagen bei der Reaktion bei 215-220 C, Sumpftemperaturen bei 188-196 C, die Kopftemperaturen stiegen bis auf ca. 158 C an. Salzabtrennung: Bevor das Reaktionswasser entfernt wird, ist unbedingt das (zum Teil ausgefallene) Ammoniumsalz zu entfernen, da dieses ansonsten whrend der Zielprodukt-Destillation in den Gasraum sublimiert und sich am Ende mit Gehalten von 2-3percent im Produkt-Destillat wiederfindet. Der Kolben mit dem Reaktionsdestillat (342 g) wurde im Labor mit einem auf 125 C beheizten Khler versehen und bei Sumpftemperaturen bis 60 C (lbad bis 68 C) und Kopftemperaturen bis 39 C von ca. 15 g Ammoniumsalz befreit. Zeitdauer 1,5 h. Der Rckstand aus 4-Methylpyrimidin, Wasser und Methanol nach der Salzabtrennung betrug 327 g. Die 4-Methylpyrimidin-Gehalte lagen typischerweise bei 34-36 Massenpercent. Der Wasseranteil bei ca. 12percent. Wasserabtrennung und Destillation: Um das Wasser aus dem Gemisch von 4-Methylpyrimidin (ca. 34percent), Wasser (ca. 12percent) und Methanol zu entfernen, wurde zum Rckstand der Salzabtrennung (327 g) eine Menge von 250 g Trimethylorthoformiat (TMOF) (2.35 mol) gegeben und das Gemisch 30 min bei RT gerhrt. Die anschlieende LeichtsiederDestillation erfolgte bei Normaldruck (Abnahme 5 : 1) an einer 60 cm-Fllkrperkolonne (mit Moltifill-Fllkrpern, 10 theor. Bden). Die lbadtemperatur wurde hierbei von 89 auf 160 C erhht. Die Sumpftemperatur stieg dabei von 69 auf 126 C und die Kopftemperatur von 34 auf 65 C, um dann wieder abzufallen (Fraktion 1, ca. 340 g). Die Zielprodukt-Destillation wurde bei 80 mbar an derselben Kolonne durchgefhrt. Im Vorlauf wurde die lbadtemperatur von 96 auf ca. 120 C hochgefahren, wobei die Sumpftemperatur von 66 auf 81 C stieg. Die Kopftemperatur stieg dabei von 31 auf 69 C an (Fraktion 2, ZP-Vorlauf, ca. 16 g). Im Hauptlauf (lbadtemp. 122-162 C, Sumpftemp. 80-128 C, Kopftemp. 69-72 C) erhielt man bei Einsatz von Vor- und Nachlufen (ca. 35 g) eines anderen, gleichartig gefahrenen Ansatzes ca. 111 g Zielprodukt mit einer Reinheit nach GC von > 99percent. Dies entspricht einer Ausbeute von 79percent an 4-Methylpyrimidin (Fraktion 3, ZP-Hauptlauf). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 180℃; und Erwaermen des Reaktionsprodukts mit wss.Salzsaeure; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 160 - 170℃; Erhitzen des Reaktionsgemisches mit verd. wss. HCl; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 160 - 170℃; Erwaermen des Reaktionsprodukts mit wss. HCl; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 170℃; Erwaermen des Reaktionsprodukts mit wss. Salzsaeure; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 180℃; Kochen des Reaktionsprodukts mit konz.HCl; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 180 - 185℃; Kochen des Reaktionsprodukts mit konz.HCl; | ||
at 180 - 185℃; Kochen des Reaktionsprodukts mit wss.-aethanol.KOH; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 180 - 185℃; Kochen des Reaktionsprodukts mit konz.HCl; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With formic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With formic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With formamide at 185℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With alkali at 360℃; es entsteht Alkalicyanid; | ||
distn. above 175°C; | ||
distn. above 175°C; |
With alkali at 360℃; es entsteht Alkalicyanid; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With nitrobenzene at 160 - 185℃; Kochen des Reaktionsprodukts mit konz.HCl; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetralin; ethylene glycol at 140℃; unter staendigem Neutralisieren mit Ameisensaeure und Erwaermen des Reaktionsprodukts mit aethanol. Natronlauge; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
nachfolgende Hydrolyse; | ||
anschl.Hydrolyse; | ||
With acetic acid at 155℃; |
Verseifen des entstehenden Formylderivates mittels siedender Salzsaeure; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With formic acid at 190℃; for 19h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | at 220℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | at 220℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With hydrogen In methanol; N,N-dimethyl-formamide for 0.166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogen In methanol; N,N-dimethyl-formamide for 0.166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With formic acid; formamide at 185 - 190℃; for 3.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In methanol for 1h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With hydrogen In methanol for 1h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In methanol; formic acid Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In methanol; formic acid Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | In methanol; water for 16h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53.5% | In N,N-dimethyl-formamide; toluene at 150 - 170℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | In xylene for 37h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 180℃; und Erwaermen des Reaktionsgemisches mit wss.-aethanol. Natronlauge; Isolierung ueber das Sulfat und das Toluol-sulfonat-(4); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 180℃; und Erwaermen des Reaktionsgemisches mit wss.-aethanol. Natronlauge; Isolierung ueber das Sulfat und ueber das Oxalat; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 160℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water; nickel at 125 - 200℃; Hydrogenation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonia; water at 160 - 220℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | at 190℃; for 3.5h; | Beispiel; Reaktion von Formamid und 4,4-Dimethoxy-2-butanon: Im trockenen Doppelmantel-Glasreaktor wurden 272 g ( 6.0 mol) Formamid vorgelegt und bei guter Rhrung auf 190 C (Sumpftemperatur) erhitzt. Innerhalb von 3 h wurden dann 209 g (1,5 mol) 95%iges 4,4-Dimethoxy-2-butanon mit Hilfe einer Schlauchpumpe kontinuierlich zudosiert. Gleichzeitig wurden ber Kopf ber ein einfaches, ummanteltes Steigrohr und einen absteigenden, auf 50 C temperierten Khler, 342 g eines gelben Reaktionsdestillates abgenommen, das aus Methanol, Wasser, 4-Methylpyrimidin und Ammoniumformiat bestand. Die Kopftemperatur fiel fast unmittelbar nach Ende der Dosierung von ca. 158 C deutlich ab. Anschlieend lie man noch 30 min nachreagieren. Das bei der Reaktion als Nebenprodukt gebildete Ammoniumformiat (ca. 15 g) neigt dazu, sich im Gasraum niederzuschlagen bzw. auf der Khlseite bei zu starker Khlung auszufallen. Bei der genannten 4,4-Dimethoxy-2-butanon-Dosierrate splte der Destillatstrom das Salz in die Vorlage. Die lbadtemperaturen lagen bei der Reaktion bei 215-220 C, Sumpftemperaturen bei 188-196 C, die Kopftemperaturen stiegen bis auf ca. 158 C an. Salzabtrennung: Bevor das Reaktionswasser entfernt wird, ist unbedingt das (zum Teil ausgefallene) Ammoniumsalz zu entfernen, da dieses ansonsten whrend der Zielprodukt-Destillation in den Gasraum sublimiert und sich am Ende mit Gehalten von 2-3% im Produkt-Destillat wiederfindet. Der Kolben mit dem Reaktionsdestillat (342 g) wurde im Labor mit einem auf 125 C beheizten Khler versehen und bei Sumpftemperaturen bis 60 C (lbad bis 68 C) und Kopftemperaturen bis 39 C von ca. 15 g Ammoniumsalz befreit. Zeitdauer 1,5 h. Der Rckstand aus 4-Methylpyrimidin, Wasser und Methanol nach der Salzabtrennung betrug 327 g. Die 4-Methylpyrimidin-Gehalte lagen typischerweise bei 34-36 Massen%. Der Wasseranteil bei ca. 12%. Wasserabtrennung und Destillation: Um das Wasser aus dem Gemisch von 4-Methylpyrimidin (ca. 34%), Wasser (ca. 12%) und Methanol zu entfernen, wurde zum Rckstand der Salzabtrennung (327 g) eine Menge von 250 g Trimethylorthoformiat (TMOF) (2.35 mol) gegeben und das Gemisch 30 min bei RT gerhrt. Die anschlieende LeichtsiederDestillation erfolgte bei Normaldruck (Abnahme 5 : 1) an einer 60 cm-Fllkrperkolonne (mit Moltifill-Fllkrpern, 10 theor. Bden). Die lbadtemperatur wurde hierbei von 89 auf 160 C erhht. Die Sumpftemperatur stieg dabei von 69 auf 126 C und die Kopftemperatur von 34 auf 65 C, um dann wieder abzufallen (Fraktion 1, ca. 340 g). Die Zielprodukt-Destillation wurde bei 80 mbar an derselben Kolonne durchgefhrt. Im Vorlauf wurde die lbadtemperatur von 96 auf ca. 120 C hochgefahren, wobei die Sumpftemperatur von 66 auf 81 C stieg. Die Kopftemperatur stieg dabei von 31 auf 69 C an (Fraktion 2, ZP-Vorlauf, ca. 16 g). Im Hauptlauf (lbadtemp. 122-162 C, Sumpftemp. 80-128 C, Kopftemp. 69-72 C) erhielt man bei Einsatz von Vor- und Nachlufen (ca. 35 g) eines anderen, gleichartig gefahrenen Ansatzes ca. 111 g Zielprodukt mit einer Reinheit nach GC von > 99%. Dies entspricht einer Ausbeute von 79% an 4-Methylpyrimidin (Fraktion 3, ZP-Hauptlauf). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In methanol at 65℃; for 2.5h; | A.9.D To a solution of 3-(Amino-oxazol-2-yl-methyl)-pyrrolidine-1-carboxylic acid benzyl ester (0.65 g, 2.2 mmol) in methanol (10 mL) was added ammonium formate (0.68 g, 11 mmol) and 10% palladium on carbon (0.70, 0.65 mmol). The reaction mixture was heated at 65 C for 2.5 hours, cooled to room temperature, and filtered. The filtrate was concentratedin vacuo to afford the title compound (0.36 g, 100%). 1H NMR (400 MHz,CDC13) 8 7.95 (s, 1H), 7.14 (s, 1H), 4.04- 3.92 (m, 1H), 3.39-2. 58 (m,7H), 2.18-1. 51 (m, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide In ethanol | 2 4-[4-(4-fluorophenyl)-4-phenylbutyl]-1H-imidazole EXAMPLE 2 4-[4-(4-fluorophenyl)-4-phenylbutyl]-1H-imidazole A concentrated water solution of ammoniumformate (0,98 g, 15,6 mmol) is added dropwise to the boiling mixture of 1-benzyl-5-[4-(4-fluorophenyl)-4-phenylbutyl]-1H-imidazole (1,5 g, 3,9 mmol) and 10% Pd/C (0,156 g) in 16 ml of 50% ethanol. The mixture is refluxed for 2 hours. The catalyst is filtrated off and the solvent is evaporated. 2M NaOH is added and the product is extracted into ethyl acetate. The ethyl acetate phase is dried and evaporated to dryness to give the product. Yield 1,02 g. Melting point of the hydrochloride salt (from ethyl acetate) is 175°-182° C. 1 H NMR (as HCl-salt, MeOH-d4): 1.40-1.90 (m, 2H), 1.90-2.30 (m, 2H), 2.75 (t, 2H), 3.96 (t, 1H), 6.85-7.36 (m, 10H), 8.74 (d, 1H) | |
With sodium hydroxide In ethanol | 2 4-[4-(4-fluorophenyl)-4-phenylbutyl]-1H-imidazole Example 2 4-[4-(4-fluorophenyl)-4-phenylbutyl]-1H-imidazole A concentrated water solution of ammoniumformate (0,98 g, 15,6 mmol) is added dropwise to the boiling mixture of 1-benzyl-5-[4-(4-fluorophenyl)-4-phenylbutyl]-1H-imidazole (1,5 g, 3,9 mmol) and 10 % Pd/C (0,156 g) in 16 ml of 50 % ethanol. The mixture is refluxed for 2 hours. The catalyst is filtrated off and the solvent is evaporated. 2 M NaOH is added and the product is extracted into ethyl acetate. The ethyl acetate phase is dried and evaporated to dryness to give the product. Yield 1,02 g. Melting point of the hydrochloride salt (from ethyl acetate) is 175-182°C. 1H NMR (as HCl-salt, MeOH-d4): 1.40-1.90 (m, 2H), 1.90-2.30 (m, 2H), 2.75 (t, 2H), 3.96 (t, 1H), 6.85-7.36 (m, 10H), 8.74 (d, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; acetic acid In conc. acetic acid; diethyl ether; dichloromethane | 10.d d d 4-[1,4-bis(4-fluorophenyl)butyl]-1H-imidazole 1-benzyl-5-[1,4-bis(4-fluorophenyl)-1-hydroxybutyl]-1H-imidazole (10 g) is dissolved in conc. acetic acid (100 ml). Into the solution is added 0,1 g of palladium on carbon and 0,8 g of ammoniumformate. The mixture is refluxed for an hour and cooled to room temperature. The solution is filtered through silicous earth. The acetic acid filtrate is evaporated, the residue is dissolved in methylene chloride and washed once with 2M aqueous sodium hydroxide solution and once with water. The methylene chloride solution is dried with sodium sulphate and evaporated under reduced pressure. The product is then made to hydrochloride salt with dry hydrogen chloride in diethylether. M.p. 135°-137° C. 1 H NMR (as base, CDCl3): 1.4-1.65 (m, 2H), 1.8-1.95 (m, 1H), 2.05-2.2 (m, 1H), 2.5-2.65 (m, 2H), 3.87 (t, 1H), 6.7 (s, 1H), 6.8-7.2 (m, 8H), 7.5 (s, 1H) | |
With hydrogenchloride; acetic acid In conc. acetic acid; diethyl ether; dichloromethane | 10.d d) d) 4-[1,4-bis(4-fluorophenyl)butyl]-1H-imidazole 1-benzyl-5-[1,4-bis(4-fluorophenyl)-1-hydroxybutyl]-1H-imidazole (10 g) is dissolved in conc. acetic acid (100 ml). Into the solution is added 0,1 g of palladium on carbon and 0,8 g of ammoniumformate. The mixture is refluxed for an hour and cooled to room temperature. The solution is filtered through silicous earth. The acetic acid filtrate is evaporated, the residue is dissolved in methylene chloride and washed once with 2 M aqueous sodium hydroxide solution and once with water. The methylene chloride solution is dried with sodium sulphate and evaporated under reduced pressure. The product is then made to hydrochloride salt with dry hydrogen chloride in diethylether. M.p. 135-137 °C. 1H NMR (as base, CDCl3): 1.4-1.65 (m, 2H), 1.8-1.95 (m, 1H), 2.05-2.2 (m, 1H), 2.5-2.65 (m, 2H), 3.87 (t, 1H), 6.7 (s, 1H), 6.8-7.2 (m, 8H), 7.5 (s, 1H) Using the same method for example the following compounds included in the invention were prepared: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate In acetic acid | 33 EXAMPLE 33 EXAMPLE 33 A mixture of 7-[(1-benzyl-1H-2,5-dimethylimidazol-4-yl)(hydroxy)methyl]-8,9-dihydro-10-methylpyrido[1,2-a]indol-6(7H)-one (1.70 g), ammoniumformate (7.78 g) and 10% palladium on carbon (0.5 g) in acetic acid (30 ml) was stirred at 120° C. for 4 hours. After filtration of the catalyst, the filtrate was evaporated in vacuo. The residue was diluted with chloroform, washed with 10% aqueous solution of sodium hydrogencarbonate, and dried over anhydrous magnesium sulfate. After the solvent was evaporated in vacuo, the residue was subjected to column chromatography on silica gel (10% methanol-chloroform). Fractions containing the product were combined and evaporated in vacuo. The residue was crystallized from ethyl acetate to give 8,9-dihydro-10-methyl-7-[(2,5-dimethyl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-one (0.36 g). mp: 219°-221° C. IR (Nujol): 1690, 1620, 1545 cm-1 NMR (DMSO-d6, δ): 1.6-1.85 (1H, m), 1.9-2.1 (1H, m), 2.05 (3H, s), 2.13 (3H, s), 2.19 (3H, s), 2.5-2.8 (2H, m), 2.9-3.2 (3H, m), 7.2-7.3 (2H, m), 7.4-7.5 (1H, m), 8.3-8.4 (1H, m) MS (m/e): 307 (M30) | |
With sodium hydrogencarbonate In acetic acid | 33 EXAMPLE 33 EXAMPLE 33 A mixture of 7-[(1-benzyl-1H-2,5-dimethylimidazol-4-yl)(hydroxy)methyl]-8,9-dihydro-10-methylpyrido[1,2-a]-indol-6(7H)-one (1.70 g), ammoniumformate (7.78 g) and 10% palladium on carbon (0.5 g) in acetic acid (30 ml) was stirred at 120° C. for 4 hours. After filtration of the catalyst, the filtrate was evaporated in vacuo. The residue was diluted with chloroform, washed with 10% aqueous solution of sodium hydrogencarbonate, and dried over anhydrous magnesium sulfate. After the solvent was evaporated in vacuo, the residue was subjected to column chromatography on silica gel (10% methanol-chloroform). Fractions containing the product were combined and evaporated in vacuo. The residue was crystallized from ethyl acetate to give 8,9-dihydro-10-methyl-7-[(2,5-dimethyl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-one (0.36 g). mp: 219°-221° C. IR (Nujol): 1690, 1620, 1545 cm-1 NMR (DMSO-d6, δ): 1.6-1.85 (1H, m), 1.9-2.1 (1H, m), 2.05 (3H, s), 2.13 (3H, s), 2.19 (3H, s), 2.5-2.8 (2H, m), 2.9-3.2 (3H, m), 7.2-7.3 (2H, m), 7.4-7.5 (1H, m), 8.3-8.4 (1H, m) MS (m/e): 307 M+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium hydroxide; formic acid; ammonia | 7 EXAMPLE 7 EXAMPLE 7 Into a round-bottom flask with a volume of 250 ml 54.2 g. (1.0 mole) of 85 percent formic acid are introduced and 69.4 g. (1.0 mole) of 24.5 percent ammonium hydroxide solution are added. The formed ammonium-formate solution is heated to 180° C. while adding gaseous ammonia steadily and under stirring so that the water brought in with the solutions and formed in the reaction is removed via the distillation apparatus connected to the round-bottom flask. When the temperature of 180° C. is reached the addition of gaseous ammonia is stopped. Meanwhile, hydrazine-formate is prepared from 70.5 g. of 71 percent (1.0 mole) hydrazine hydrate and from 54.2 g. (1.0 mole) of 85 percent formic acid and to this 34.7 g. (0.5 moles) of 24.5 percent ammonium hydroxide solution are added. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride In ethanol-water-solution; diethyl ether; water | 1.b b) b) 4-[2-(4-fluorophenyl)-4-phenylbutyl]-1H-imidazole 1-benzyl-5-[2-(4-fluorophenyl)-4-phenyl-1-butenyl]-1H-imidazole (4,58 g, 0,0012 mol) is dissolved in ethanol-water-solution (25:15). 0,46 g of 10 % Pd/C and 3,8 g (0,06 mol) of ammoniumformate in 15 ml of water is added to the mixture. After refluxing for 2 hours the mixture is filtered and the filtrate is evaporated to dryness. The residue is dissolved into methylene chloride and washed a few times with water. Methylene chloride is evaporated and the residue is dissolved into 2 M hydrogen chloride solution. The solution is extracted twice with diethyl ether. The water layer is made alkaline and extracted with methylene chloride. The methylene chloride phase is dried and evaporated to dryness. The product is then made to hydrochloride salt with dry hydrogen chloride gas in diethyl ether. MS: 294 (12, M+.), 203 (36), 190 (28), 109 (28), 91 (100), 82 (42) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: ethyl 4-oxocyclohexaneacetate With sodium hydroxide In ethanol at 20℃; for 1h; Stage #2: With diethoxyphosphoryl-acetic acid ethyl ester; sodium ethanolate In ethanol at 0 - 20℃; for 2h; Stage #3: ammonium formate With hydrogenchloride; acetic acid more than 3 stages; | 13.A A three liter round bottom flask was charged with ethyl (4-oxocyclohexyl)acetate (10Og, 0.588 mol) and ethanol (400 mL). Sodium hydroxide (25.8 g, 0.645 mol) was added, and the reaction was stirred at room temperature for 1 hour. Next, triethyl phosphonoacetate (128 mL, 0.645 mol) was added, and the reaction was then cooled to 0 0C. A solution of NaOEt in EtOH (21% solution, 242 mL) was added dropwise to the reaction over 1 hour. The reaction was warmed to room temperature and stirred for 1 hour. HOAc (84 mL) was added, followed by ammonium formate (74 g) and 5% Pd/C (10 g). The reaction was heated to 600C for 6 hours and then cooled to room temperature. The solids were filtered off and the filtrate was concentrated. The residue was taken up in EtOAc (2 L) and washed with IN HCl (2 x 500 mL), H2O (500 mL), and brine (500 mL). The organic layer was concentrated to an oil and azeotroped with toluene (2 L). The residue was purified by flash chromatography on silica gel (0 to 50% EtOAc/Hexanes containing 1% HOAc). This afforded 4-(2-ethoxy-2-oxoethyl)cyclohexanecarboxylic acid as a mixture of cis and trans isomers. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water In hydrogenchloride at 35 45 and 65°C; | ||
With hydrogen bromide In hydrogen bromide | ||
explosive decomposition; |
explosive decomposition; | ||
>99 | With H2O In hydrogenchloride complete hydrolysis; | |
With H2O In hydrogenchloride at 35 45 and 65°C; | ||
With HBr In hydrogen bromide aq. HBr; | ||
>99 | With water In hydrogenchloride complete hydrolysis; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In diethyl ether introduction of dry NH3 into ethereal soln. of HCO2H; recrystallizing from ethanol; | ||
In not given introduction of gaseous NH3 into 90 % HCO2H soln., finishing by higher temperature; recrystallizing from dry alcohol, drying over H2SO4 in vacuum desiccator; | ||
In water neutralization of aq. HCO2H with NH3, evaporation, concentration in vacuo; |
In not given introduction of gaseous NH3 into 90 % HCO2H soln., finishing by higher temperature; recrystallizing from dry alcohol, drying over H2SO4 in vacuum desiccator; | ||
In diethyl ether introduction of dry NH3 into ethereal soln. of HCO2H; recrystallizing from ethanol; | ||
In methanol by the react. of formic acid with ammonia in methanol; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | In 1,4-dioxane byproducts: H2, NaO2CH; (inert atmosphere); dioxane added to NaBH4 and NH4O2CH, stirred vigorously at 40°C for ca 2 h; cooled to room temp., filtered, washed (dioxane); the combined filtratesconcd. (vac.); elem. anal.; | |
93% | In tetrahydrofuran (inert atmosphere); at 25-40°C for 2-25 h; | |
In tetrachloromethane (inert atmosphere); at 40°C for 13 h; |
In dichloromethane (inert atmosphere); at 40°C for 15 h; | ||
In diethylene glycol dimethyl ether (inert atmosphere); at 40°C for 4 h; | ||
In ethyl acetate (inert atmosphere); at 40°C for 9.5 h; | ||
In N,N-dimethyl-formamide (inert atmosphere); at 40°C for 8 h; | ||
In toluene (inert atmosphere); at 40°C for 7 h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water In gas by higher temperature; | ||
In water | ||
With H2O In neat (no solvent, gas phase) by higher temperature; |
In water | ||
With water In gas by higher temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In gas | ||
in present of catalysts; | ||
With H2 In water |
in present of catalysts; | ||
In neat (no solvent, gas phase) | ||
With hydrogen In water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With C2H5OH In ethanol to soln. of Cu(CF3COO)2 in EtOH was added a soln. of NH2(CH2)3OH in EtOH and a soln. of HCOONH4 in EtOH, kept at room temp. for 1 d; ppt. filtered, washed with EtOH, acetone; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With tributylphosphane In tetrahydrofuran (N2); addn. of phosphine to a soln. of palladium complex and ammonium salt in THF, stirring for 5 min at room temp., addn. of a soln. of chromium complex in THF, stirring for 28 h at room temp.; evapn., chromy (SiO2, Et2O/pentane 1:4), dissolving in pentane, filtration, evapn., recrystn. (pentane); elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With catalyst: Pd-C In methanol; dichloromethane under N2; Pd-C and HCO2NH4 added at room temp. to soln. of Fe complex inCH2Cl2-MeOH; stirred at room temp. overnight; filtered over Celite; solvent evapd.; dissolved in AcOEt; washed (brine); aq. phase extd. (AcOEt); combined org. phase washed (H2O); dried (Na2SO4); evapd.; purified by column chromy. (silica gel, AcOEt); elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With catalyst: Pd-C In methanol; N,N-dimethyl-formamide under N2; Pd-C and HCO2NH4 added at room temp. to soln. of Fe complex inDMF-MeOH; stirred for 2 h; filtered over Celite; solvent evapd.; dissolved in CH2Cl2; washed with brine; org. phase dried (Na2SO4); evapd.; taken up with CH2Cl2; filtered;ppt. washed with CH2Cl2; dried; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With catalyst: Pd-C In methanol under N2; HCO2NH4 and Pd-C added at room temp. to soln. of Fe complex inMeOH; stirred for 25 h; filtered through Celite; evapd. under vac.; purified by column chromy. (silica gel, CH2Cl2-MeOH 1:1); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | In methanol by the react. of Mn-contg. compd. with (NH4)(HCOO) in MeOH; the mixed soln. was kept undisturbed; crystals were harvested after 1 d; crystals were washed with methanol and dried under vac.; elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With catalyst:Pd/C In methanol High Pressure; addn. of palladium catalyst to soln. of mixture of ammonium formate and iron compd. in methanol, refluxing for 6 h; filtration, concn., chromy. (SiO2, hexane/triethylamine (100:0-80:20)), elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In methanol MeOH soln. of (NH4)(HCOO) was placed at the bottom of a glass tube and at this soln. MeOH was gently added followed by layering MeOH soln. of Co-contg. compd.; the tube was sealed and kept undisturbed; crystals were harvested after 5 d; crystals were washed with methanol and dried under vac.; elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With N2H4; NH4NpO2(OOCH)2 In ethanol; water to aq. Pu-compd. a 2.5-3-fold volume of 8 M NH4OOCH and equimolar amountof 0.4-1 M N2H4 added, stirred for 10-15 s, EtOH and Np-compd. added; coagulated for 20-30 min, filtered, washed with EtOH, dried in an air stream for ca. 2 h, elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With 20% palladium hydroxide-activated charcoal; hydrogen In methanol at 40℃; for 48h; | 3.2 RRN 182Step 2. Synthesis of N-[(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(6-methoxypyridin-3-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C38) Step 2. Synthesis of N-[(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(6-methoxypyridin-3-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C38) Ammonium formate (97%, 32 mg, 0.49 mmol) was added to a mixture of C37 (116 mg, 0.235 mmol) and palladium hydroxide (20% on carbon, wet, 200 mg) in methanol (10 mL), and the reaction mixture was vigorously shaken at 40° C. under hydrogen (45 psi) for 24 hours. Additional palladium hydroxide (50 mg) was added, and hydrogenation was continued at 40° C. for an additional 24 hours. The reaction mixture was filtered through diatomaceous earth, and the filter pad was washed sequentially with methanol, dichloromethane and ethyl acetate; the combined filtrates were concentrated in vacuo. Purification via chromatography on silica gel (Gradient: 0% to 100% ethyl acetate in hexanes) provided the product. Starting material C37 (17 mg) was also isolated. Yield, corrected for recovered starting material: 30 mg, 60 μmol, 30%. LCMS m/z 496.3 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: C24H30ClN9O4; ethyl iodide In acetonitrile at 120℃; for 3h; Microwave irradiation; Sealed tube; Stage #2: ammonium formate In water; acetonitrile | 3.1 Example 3.1 Example 3.1 A mixture of Intermediate XVIII.2 (0.15 g; 0.248mmol) and ethyl iodide (0.204 mL; 2.48 mmol) in ACN (4 ml) is stirred for 2 h at 120°C (microwave heating, closed vessel). Further ethyl iodide (0.102 mL;1 .24 mmol) is added and the mixture is stirred for one further hour at 120°C. The mixture is purified by RP-HPLC (water-ACN; modifier ammonium formate) to yield the title com- pound. C26H35CIN9O4 x HC02 ESI Mass spectrum: m/z = 572 [M+] HPLC analytics: RT = 3.27 min (HPLC method 5) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | Stage #1: diisopropylaethylamonium N,N,2,2-tetramethyl-4-oxo-N-(2-(phosphonooxy)ethyl)-3,8,11,14-tetraoxa-5-azahexadecan-16-aminium; cytidine-5'-monophosphomorpholidate 4-morpholine-N,N'-dicyclohexylcarboxamidine salt With pyridine; 1H-tetrazole at 20℃; for 48h; Inert atmosphere; Stage #2: ammonium formate In water; acetonitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | Stage #1: diisopropylaethylamonium 2,2,11,11-tetramethyl-4-oxo-3,8-dioxa-5,11-diazatridecan-11-ium-13-yl phosphate; cytidine-5'-monophosphomorpholidate 4-morpholine-N,N'-dicyclohexylcarboxamidine salt With pyridine; 1H-tetrazole at 20℃; for 72h; Inert atmosphere; Stage #2: ammonium formate In water; acetonitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
23% | Stage #1: 1,4-diaza-bicyclo[2.2.2]octane; 2-[[4-(3-chloropropoxy)-2,6-difluorophenyl]methylsulfanyl]-N-(3,4-dimethoxyphenyl)-3-(4-fluorophenyl)-N-methylimidazol-4-amine In acetonitrile at 100℃; for 0.5h; Microwave irradiation; Stage #2: ammonium formate | 25 2-[[4-[3-(l-aza-4-azoniabicyclo[2.2.2]octan-4-yl)propoxy]-2,6-difluoro- phenyl]methylsulfanyl]-N-(3,4-dimethoxyphenyl)-3-(4-fluorophenyl)-N-methyl- imidazol-4-amine ; formate 2-[[4-[3-(l-aza-4-azoniabicyclo[2.2.2]octan-4-yl)propoxy]-2,6-difluoro- phenyl]methylsulfanyl]-N-(3,4-dimethoxyphenyl)-3-(4-fluorophenyl)-N-methyl- imidazol-4-amine ; formateIntermediate 6 (225 mg, 370 μιηο) and DABCO (112 mg, 1.0 mmol) are dissolved in dry acetonitrile (3.7 mL). Reaction mixture is then heated under microwave irradiation at 100 °C for 30 min. It is then evaporated to dryness and purified by preparative HPLC (ammonium formate buffer, pH = 9.2) to give 60 mg of a pale orange powder corresponding to the expected product (23%).MS [M]+ m/z = 654.21H-NMR (CDCI3) : δ (ppm) 2.31 (brs, 2H) ; 2.94 (s, 3H) ; 3.32 (brs, 6H) ; 3.48-3.82 (m, 14H) ; 3.94 (s, 2H) ; 4.06 (brs, 2H) ; 6.16 (dd, J = 8.7 Hz, J = 2.7 Hz, 1H) ; 6.27 (d, J = 2.7 Hz, 1H) ; 6.35-6.47 (m, 2H) ; 6.71 (d, J = 8.8 Hz, 1H) ; 6.93-7.11 (m, 5H) ; 8.60 (s, 1H).13C-NMR (CDCl3) : δ (ppm) 22.1 ; 25.7 ; 40.3 ; 45.3 ; 52.6 ; 55.9 ; 56.5 ; 61.8 ; 65.2 ; 98.2- 98.8 (m) ; 100.1 ; 105.9 ; 106.0 (t, J = 20.1 Hz) ; 112.5 ; 116.0 (d, J = 22.9 Hz) ; 123.9 ; 129.3 (d, J = 8.8 Hz) ; 130.9 (d, J = 3.2 Hz) ; 137.8 ; 140.1 ; 142.8 ; 143.1 ; 149.6 ; 159.0 (t, J = 14.1 Hz) ; 161.6 (dd, J = 248.2 Hz, J = 11.0 Hz) ; 162.3 (d, J = 249.3 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14% | With formic acid at 100℃; for 3h; | 51.2 Step 2. Methyl 4-benzyloxazole-5-carboxylate A 250-mE round-bottom flask was charged with methyl 2-chloro-3-oxo-4-phenylbutanoate (Step 1, 2.26 g, 9.97 mmol), formic acid (30 mE) and ammonium formate (2.31 g, 30.00 mmol). The resulting solution was stirred for 3 hat 100° C. The reaction was cooled to 23° C. and quenched with saturated sodium bicarbonate (50 mE). The product was extracted with ethyl acetate (3x50 mE). The combined organic layers were washed with brine (50 mE), dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by column chromatography eluting with ethyl acetate/petroleum ether (1:50 to 1:8 v/v) to afford methyl 4-benzyloxazole-5-carboxylate (300 mg, 14%) as a yellow solid. ECMS: (ESI) mlz 218 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: manganese(II) chloride tetrahydrate; ammonium formate; water; 4-(1H-tetrazol-5-yl)benzoic acid; N,N-dimethyl-formamide Sonication; Stage #2: at 120℃; for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | Stage #1: C28H34F4N6O5S With trifluoroacetic acid at 20℃; for 0.333333h; Stage #2: formaldehyd With sodium acetate In methanol; water for 0.0833333h; Stage #3: ammonium formate Further stages; | 17.10 Step 10: N-(4-(2-(((1,4-trans)-4-(Dimethylamino)cyclohexyl)amino)-8-methoxy- pyrido[3,2-d]pyrimidin-6-yl)-2-fluorophenyl)-3,3,3-trifluoropropane-1-sulfonamide formate To tert-butyl N-[4-[[6-[3-fluoro-4-(3,3,3-trifluoropropylsulfonylamino)phenyl]-8- methoxy-pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carbamate (62 mg, 0.10 mmol) was added TFA (1 mL, 0.10 mmol) and the reaction was stirred at rt for 20 min. To the reaction was added toluene (5 mL) and the solvent was removed in vacuo to give the crude amine, which was dissolved in methanol (1 mL). To the solution was added NaOAc (158 mg, 1.93 mmol) followed by 37% w/w aqueous formaldehyde (96 mg, 0.96 mmol). The reaction was stirred for 5 min before addition of sodium triacetoxyborohydride (81 mg, 0.39 mmol) and stirred at rt for 20 min. The mixture was then directly purified by C18 reverse phase flash chromatography (10- 100% MeCN/10 mM aqueous ammonium formate, pH = 3.8) to pro- vide the title compound (16 mg, 27% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50 mg | Stage #1: formaldehyd; N-(4-(2-(((1,4-trans)-4-Aminocyclohexyl)amino)-8-methylpyrido[3,2-d]pyrimidin-6-yl)-2-fluorophenyl)-3,3-difluorobutane-1-sulfonamide 2,2,2-trifluoroacetate With sodium acetate In methanol; water at 20℃; for 0.0833333h; Stage #2: With methanol; sodium tris(acetoxy)borohydride In water at 20℃; for 1h; Stage #3: ammonium formate In water; acetonitrile | 12.5 Step 5: N-(4-(2-(((1,4-trans)-4-(Dimethylamino)cyclohexyl)amino)-8-methylpyr- ido[3,2-d]pyrimidin-6-yl)-2-fluorophenyl)-3,3-difluorobutane-1-sulfonamide formate To a solution of N-[4-[2-[(4-Aminocyclohexyl)amino]-8-methyl-pyrido[3,2-d]py- rimidin-6-yl]-2-fluoro-phenyl]-3,3-difluoro-butane-1-sulfonamide; 2,2,2-trifluoroacetic acid (83 mg, 0.13 mmol) in methanol (1.1 mL) was added sodium acetate (64 mg, 0.78 mmol) fol- lowed by 37% w/w aqueous formaldehyde (0.16 mL, 1.96 mmol). The mixture was stirred at rt for 5 min then sodium triacetoxyborohydride (109 mg, 0.52 mmol) was added and the mix- ture was stirred at rt. After 1 h, 2/3 of volatiles removed under reduced pressure and the crude residue was purified by C18 reverse phase flash chromatography (20- 80% MeCN/10 mM aqueous ammonium formate, pH = 3.8) to provide the title product (50 mg, 69% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | Stage #1: (3S,5S)-tert-butyl 3-((8-ethyl-6-(3-fluoro-4-(3,3,3-trifluoropropylsulfonamido)phenyl)pyrido[3,2-d]pyrimidin-2-yl)amino)-5-fluoropiperidine-1-carboxylate With hydrogenchloride In 1,4-dioxane at 20℃; for 2h; Stage #2: ammonium formate In water; acetonitrile | 18.4 Step 4: N-(4-(8-Ethyl-2-(((3S,5S)-5-fluoropiperidin-3-yl)amino)pyrido[3,2-d]py- rimidin-6-yl)-2-fluorophenyl)-3,3,3-trifluoropropane-1-sulfonamide formate Prepared according to Example 14 (Compound 115) step 4 using (3S,5S)-tert-bu- tyl 3-((8-ethyl-6-(3-fluoro-4-(3,3,3-trifluoropropylsulfonamido)phenyl)pyrido[3,2-d]pyrim- idin-2-yl)amino)-5-fluoropiperidine-1-carboxylate (69 mg, 0.11 mmol) and 4M HCl in diox- ane (1.0 mL, 4.0 mmol) to provide the title product (37 mg, 59% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | Stage #1: (3S,5S)-tert-butyl 3-((6-(4-amino-2-fluorophenyl)-8-ethylquinazolin-2-yl)amino)-5-fluoropiperidine-1-carboxylate; benzenesulfonyl chloride With pyridine at 20℃; for 1h; Stage #2: With hydrogenchloride In 1,4-dioxane at 20℃; for 1h; Stage #3: ammonium formate In water; acetonitrile | 1016.8 Step 8: N-(4-(8-Ethyl-2-(((3S,5S)-5-fluoropiperidin-3-yl)amino)quinazolin-6-yl)- 3-fluorophenyl)-1-phenylmethanesulfonamide formate To a solution of (3S,5S)-tert-butyl 3-((6-(4-amino-2-fluorophenyl)-8- ethylquinazolin-2-yl)amino)-5-fluoropiperidine-1-carboxylate (62 mg, 0.13 mmol) in pyridine (0.7 mL) was added phenylmethanesulfonyl chloride (32 mg, 0.17 mmol) and the mixture stirred at rt. After 1 h, the mixture was diluted with methanol and silica gel was added and volatiles removed under reduced pressure to adsorb the crude product onto silica gel and purified by silica flash chromatography (10% EtOAc/heptanes) to provide the sulfonamide (3S,5S)-tert-butyl 3-((8-ethyl-6-(2-fluoro-4- (phenylmethylsulfonamido)phenyl)quinazolin-2-yl)amino)-5-fluoropiperidine-1-carboxylate (56 mg, 68% yield). (3S,5S)-tert-Butyl 3-((8-ethyl-6-(2-fluoro-4- (phenylmethylsulfonamido)phenyl)quinazolin-2-yl)amino)-5-fluoropiperidine-1-carboxylate (56 mg, 0.09 mmol) thus obtained was treated with 4N HCl in dioxanes (0.6 mL, 2.4 mmol) and stirred at rt. After 1 h, volatiles removed under reduced pressure and the crude residue was purified by C18 reverse phase flash chromatography (0- 100% MeCN/10mM aqueous ammonium formate, pH = 3.8) to provide the title product (29 mg, 55% yield over two steps). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9% | With palladium 10% on activated carbon In methanol at 80℃; for 5h; Irradiation; |
Tags: 540-69-2 synthesis path| 540-69-2 SDS| 540-69-2 COA| 540-69-2 purity| 540-69-2 application| 540-69-2 NMR| 540-69-2 COA| 540-69-2 structure
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P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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