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Structure of 4023-34-1
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 4023-34-1 |
Formula : | C4H5ClO |
M.W : | 104.53 |
SMILES Code : | O=C(C1CC1)Cl |
MDL No. : | MFCD00001277 |
InChI Key : | ZOOSILUVXHVRJE-UHFFFAOYSA-N |
Pubchem ID : | 77637 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H301-H314-H226 |
Precautionary Statements: | P210-P233-P240-P241-P242-P243-P264-P270-P280-P301+P310+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P363-P370+P378-P403+P235-P405-P501 |
Class: | 8(3) |
UN#: | 2920 |
Packing Group: | Ⅱ |
* 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 |
---|---|---|
80% | Reference Example 1 Production of methyl 3-cyclopropyl-3-oxopropionate Merdramic acid (50 g; 347 mmols) was dissolved in chloroform (550 ml), and pyridine (56 g; 700 mmols) was added thereto. Subsequently, a solution of cyclopropanecarboxylic acid chloride (40 g; 383 mmols) in chloroform (50 ml) was added dropwise thereto at a temperature of 10C or lower while cooling in an ice-bath. After completion of the dropwise addition, the mixture was stirred for further 1 hour under cooling in the ice-bath, then at room temperature for 1 hour. Subsequently, after cooling again using the ice-bath, 1N-HCL aqueous solution (500 ml) was added thereto. The reaction product was extracted with chloroform, washed with water, and dried over anhydrous sodium sulfate, followed by concentrating under reduced pressure. Then, methanol (500 ml) was added thereto to dissolve the residue, and the solution was heated for 3 hours under reflux. After cooling to room temperature, the solvent was distilled off under reduced pressure, and the residue was distilled to obtain 40 g of methyl 3-cyclopropyl-3-oxopropionate. Yield: 80% Physical properties: bp. 80C (10mmHg) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.1% | With pyridine; In dichloromethane; at 0 - 20℃; | a.2 2-te/t-Butvl-4-f4-(3-chloro-propvl)-piperazin-1-vll-6-cvclopropvl-pyrimidine; a.2.1: Methyl-2-cvclopropanovl-acetate; 48.6 g of meldrum's acid (337.4 mmol) were dissolved in 200 ml of dichloromethane at room temperature and the solution was cooled to 0C. 40 g of pyridine (506.1 mmol) were added to said solution. 35.3 g of cyclopropyl carbonic acid chloride (337.4 mmol) were then added at 0C within 1 h. The reaction mixture was stirred overnight at room temperature, washed with 1 N HCI and extracted with dichloromethane. The organic layer was washed with water, dried over magnesium sulfate, filtered and then concentrated to dryness. The oily residue was dissolved in 300 ml of methanol and stirred under reflux for 2h. The reaction mixture was concentrated to dryness and the oily residue was purified by destination at 90 C bath temperature to yield 42.7 g (71,1 %) of the title compound.MS (ESI) m/z: 143.1 [M+H]+1H-NMR (CDCI3): 5 [ppm] 3.75 (s, 3H), 3.6 (s, 2H), 2.0 (m, 1H), 1.15 (m, 2H),0.95 (m, 2H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 0 - 20℃; | Step 1 Synthesis of methyl {2-(cyclopropylcarbonyl)amino-5-trifluoromethyl}benzoate Methyl 2-amino-5-(trifluoromethyl)benzoate (0.20 g, 0.91 mmol) obtained as an intermediate for Step 1 of Example 7 was dissolved in methylene chloride (10 ml), triethylamine (0.25 ml, 1.82 mmol) and cyclopropanecarbonyl chloride (0.11 g, 1.1 mmol) were added at 0C, and the mixture was stirred overnight at room temperature. After work-up according to a conventional method, the mixture was purified by silica gel column chromatography (10% to 30% mixed solvent of ethyl acetate/hexane) to give the title compound (0.10 g, 0.35 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | To a suspension of magnesium chloride (3.3 g, 35 ml) in CH2Cl2 (15 ml) under argon at 0 C. was added methyl-3-cyclopropyl-oxopropanoate (5.0 g, 35 mmol), followed by pyridine (2.8 ml, 35 mmol). The mixture was stirred for 1 h before the addition of a solution of cyclopropylcarbonylchloride (3.2 ml, 35 mol) in CH2Cl2 (5 ml), followed by more pyridine (2.8 ml, 35 mmol) and the mixture was stirred for a further 1 h. The reaction was washed repeatedly with 6N HCl, dried (Na2SO4) and concentrated. Purification by flash column chromatography (EtOAc:n-heptane 1:9) afforded the title product (7.4 g, 99%) as a colourless oil. MS: 211.1 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With triethylamine; In 1,2-dichloro-ethane; at 20℃; | <strong>[1010120-55-4]5-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine</strong> (10 g, 50 mmol) and triethylamine (10 g, 100 mmol) in dichloroethane (200 mL) Cyclopropionyl chloride (5.7 g, 55 mmol) was added and stirred at room temperature overnight. After the reaction mixture was diluted, it was washed with water, washed with saturated brine, dried over anhydrous sodium sulfate and evaporated. Purification by silica gel column chromatography gave white solid (10 g, 76%) |
58% | Step (Hi)5-bromo-[l,2,4]triazolo[l,5-a]pyridin-2-amine (10.7g, 50mmol) was suspended in acetonitrile (200mL) and DIPEA (9.6mL, 55mmol). Cyclopropanecarbonyl chloride (5.0mL, 55mmol) and 4-(Dimethylamino)pyridine (287mg, 2.35mmol) were added in one portion and the suspension heated at 80C for 18h. After this time the solvents were removed in vacuo and the resulting solid was stirred in ammonia/methanol (2M) for 2h at rt. The solvents were removed in vacuo and the resulting solid was triturated, filtered and washed with diethyl ether (3 x lOOmL) to afford the desired compound as a white solid (8.12g, 58% ). LCMS (method A), (M+H+) 281/283, RT = 0.78min. | |
56.64% | To <strong>[1010120-55-4]5-bromo-[1,2,4] triazolo[1,5-a]pyridin-2-amine</strong>(15.00 g, 70.41 mmol) and triethylamine(21.4 g, 211.2 mmol), dissolved in acetonitrile(150 mL) was added dropwise cyclopropanecarboxylic acid chloride(8.8 g, 84.5 mmol) at 0C. After adding, the mixture was warmed to room temperature for the reaction for 16 hours. After TLC showed that the reaction was completed through monitoring, the reaction mixture was distilled under reduced pressure. The resulting residue was dissolved in an alcoholic solution of methylamine(150 mL), heated to 80C for the reaction for 1 hour, cooled, distilled under reduced pressure. The resulting residue was dissolved in mixed solution of water(100 mL) and ethyl acetate(200 mL), and the layers were separated and extracted. The combined organic phase was dried with anhydrous sodium sulfate and filtered, and the filtrate was distilled under reduced pressure. The resulting crude product was purified through silica gel column chromatography (eluting with ethyl acetate/petroleum ether =0?70%) to give N-(5-bromo-[1,2,4]triazolo[1,5-a] pyridin-2-yl)cyclopropyl carboxamide (7.2 g, 56.64% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) delta = 11.20 (br. s., 1 H), 7.68 - 7.73 (m, 1 H), 7.52 - 7.58 (m, 1 H), 7.46 - 7.51 (m, 1 H), 1.96 - 2.09 (m, 1 H), 0.82 (d, J=6.28 Hz, 4 H). MS (ESI) Calcd. for C10H9 BrN4O [M + H]+ 282, Found 282. |
To a solution of the 2-amino-triazolopyridine (3) (7.10 g, 33.3 mmol) in dry CH3CN (150 mL) at 50C is added Et3N (11.6 mL, 83.3 mmol) followed by the appropriate acid chloride (83.3 mmol). The reaction mixture is then allowed to warm to ambient temperature and stirred until all starting material (3) is consumed. If required, further Et3N (4.64 mL, 33.3 mmol) and acid chloride (33.3 mmol) may be added to ensure complete reaction. Following solvent evaporation in vacuo the resultant residue is treated with 7 N methanolic ammonia solution (50 mL) and stirred at ambient temp, (for 1-16 h) to hydrolyse any bis-acylated product. Product isolation is made by removal of volatiles in vacuo followed by trituration with Et2O (50 mL). The solids may be collected by filtration, washed with H2O (2x50 rnL), acetone (50 rnL) and Et2O (50 rnL), then dried in vacuo to give the required intermediate (4). In some cases column chromatography (petrol/EtOAc) may be required to obtain pure compounds. | ||
To a solution of the 2-amino-triazolopyridine (3) (7.10 g, 33.3 mmol) in dry CH3CN (150 mL) at 5 C. is added Et3N (11.6 mL, 83.3 mmol) followed by the appropriate acid chloride (83.3 mmol). The reaction mixture is then allowed to warm to ambient temperature and stirred until all starting material (3) is consumed. If required, further Et3N (4.64 mL, 33.3 mmol) and the acid chloride (33.3 mmol) may be added to ensure complete reaction. Following solvent evaporation in vacuo the resultant residue is treated with 7 N methanolic ammonia solution (50 mL) and stirred at ambient temp. (for 1-16 h) to hydrolyse any bis-acylated product. Product isolation is made by removal of volatiles in vacuo followed by trituration with Et2O (50 mL). The solids may be collected by filtration, washed with H2O (2×50 mL), acetone (50 mL) and Et2O (50 mL), then dried in vacuo to give the required acyl intermediate (4). In some cases column chromatography (petrol/EtOAc) may be required to obtain pure compounds. | ||
1.1.3 General Procedure for Mono-Acylation to Afford Intermediate (4) To a solution of the 2-amino-triazolopyridine (3) (7.10 g, 33.3 mmol) in dry CH3CN (150 mL) at 5 C. is added Et3N (11.6 mL, 83.3 mmol) followed by cyclopropanecarbonyl chloride (83.3 mmol). The reaction mixture is then allowed to warm to ambient temperature and stirred until all starting material (3) is consumed. If required, further Et3N (4.64 mL, 33.3 mmol) and cyclopropanecarbonyl chloride (33.3 mmol) is added to ensure complete reaction. Following solvent evaporation in vacuo the resultant residue is treated with 7 N methanolic ammonia solution (50 mL) and stirred at ambient temp. (for 1-16 h) to hydrolyse any bis-acylated product. Product isolation is made by removal of volatiles in vacuo followed by trituration with Et2O (50 mL). The solids are collected by filtration, washed with H2O (2*50 mL), acetone (50 mL) and Et2O (50 mL), then dried in vacuo to give the required bromo intermediate (4). | ||
With triethylamine; In acetonitrile; at 5 - 20℃; | Step iii : Cyclopropanecarboxylic acid (5-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-amide To a solution of the 2-amino-triazolopyridine obtained in the previous step (7.10 g, 33.3 mmol) in dry MeCN (150 mL) at 5 C. is added Et3N (11.6 mL, 83.3 mmol) followed by cyclopropanecarbonyl chloride (83.3 mmol). The reaction mixture is then allowed to warm to ambient temperature and stirred until all starting material is consumed. If required, further Et3N (4.64 mL, 33.3 mmol) and cyclopropanecarbonyl chloride (33.3 mmol) is added to ensure complete reaction. Following solvent evaporation in vacuo the resultant residue is treated with 7 N methanolic ammonia solution (50 mL) and stirred at ambient temp. (for 1-16 h) to hydrolyse any bis-acylated product. Product isolation is made by removal of volatiles in vacuo followed by trituration with Et2O (50 mL). The solids are collected by filtration, washed with H2O (2*50 mL), acetone (50 mL) and Et2O (50 mL), then dried in vacuo to give the desired compound. | |
Step iii : Cyclopropanecarboxylic acid (5-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-amide To a solution of the 2-amino-triazolopyridine obtained in the previous step (7.10 g, 33.3 mmol) in dry MeCN (150 mL) at 5 C. is added Et3N (11.6 mL, 83.3 mmol) followed by cyclopropanecarbonyl chloride (83.3 mmol). The reaction mixture is then allowed to warm to ambient temperature and stirred until all starting material is consumed. If required, further Et3N (4.64 mL, 33.3 mmol) and cyclopropanecarbonyl chloride (33.3 mmol) is added to ensure complete reaction. Following solvent evaporation in vacuo the resultant residue is treated with 7 N methanolic ammonia solution (50 mL) and stirred at ambient temp. (for 1-16 h) to hydrolyse any bis-acylated product. Product isolation is made by removal of volatiles in vacuo followed by trituration with Et2O (50 mL). The solids are collected by filtration, washed with H2O (2*50 mL), acetone (50 mL) and Et2O (50 mL), then dried in vacuo to give the desired compound. | ||
With triethylamine; In acetonitrile; at 5 - 20℃; | [0167] To a solution of the 2-amino-triazolopyridine obtained in the previous step (7.10 g, 33.3 mmol) in dry MeCN (150 mL) at 5C is added Et3N (11.6 mL, 83.3 mmol) followed by cyclopropanecarbonyl chloride (83.3 mmol). The reaction mixture is then allowed to warm to ambient temperature and stirred until all starting material is consumed. If required, further Et3N (4.64 mL, 33.3 mmol) and cyclopropanecarbonyl chloride (33.3 mmol) is added to ensure complete reaction. Following solvent evaporation in vacuo the resultant residue is treated with 7 N methanolic ammonia solution (50 mL) and stirred at ambient temp, (for 1 h-16 h) to hydro lyse any bis-acylated product. Product isolation is made by removal of volatiles in vacuo followed by trituration with Et20 (50 mL). The solids are collected by filtration, washed with H20 (2x50 mL), acetone (50 mL) and Et20 (50 mL), then dried in vacuo to give the desired compound | |
4.5 g | With pyridine; at -50℃; for 0.166667h; | Add 50mL pyridine to the reaction flask,Cyclopropane chloride (2.9 g, 28 mmol) was added dropwise to the reaction flask at -50C.Stir for 10 minutes,5-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine (5 g, 23 mmol) was then added to the reaction flaskin,The reaction was stirred overnight at room temperature.After the reaction is completed,Add 100 mL of petroleum ether to the reaction solution.FilteringFilter cake washed twice with petroleum ether, Each time 100mL,Then wash once with 100mL of waterTo get the title product,Earth gray solid 4.5g |
4 g | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0℃; for 5h; | 100 ml of 6 dichloromethane and 9 g of 12 diisopropylethylamine were added to 5 g of the product of Step 2. The mixture was cooled to 0 C in an ice bath. 6.1 g of 15 cyclopropanecarbonyl chloride was added dropwise. The mixture became clear after 1 hour of reaction. After the reaction was continued for 4 hours, the reaction system was concentrated to dryness to give an oily 16 solid. Then, a mixed solution of 7 ml of ammonia water and 43 ml of methanol was added to the oily solid under cooling in an ice salt bath, and stirred for about 3 hours. The system became a brown turbid liquid. After filtration by suction, the solid was washed with water and dried to obtain 4 g of the target. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a mixture of 8.5 g of sodium carbonate, 3.2 g of sodium hydroxide, 100 ml of water, 100 ml of THF and 5.0 g of glycine was added 7.7 g of cyclopropanecarbonyl chloride at 0C, then, the mixture was stirred at room temperature for 15 hours. Concentrated hydrochloric acid was added until pH of the mixture reached 2, and THF was distilled off under reduced pressure. To the residue was added 400 ml of ethyl acetate, and the mixture was stirred at room temperature for 3 hours.The mixture was filtrated, and 50 ml of water was added to the filtrate, and this was extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, and concentrated under reduced pressure to obtain 9.6 g of ( cyclopropanecarbonyl- amide ) -acetic acid.1 H-NMR (D SO-D6) delta: 12.49 (1H, s), 8.40-8.35 (1H, m) , 3.76 (2H, d) , 1.66-1.59 (1H, m) , 0.66 (4H, d) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
> 80% | With pyridine; In tetrahydrofuran; at 20℃; | Compounds 74 and 81 were synthesized by using the materials that have a substituent corresponding to these compounds, according to the following production scheme. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With triethylamine; In dichloromethane; for 2.0h;Cooling with ice; | N-(5-Bromo-1H-indol-7-yl)cyclopropanecarboxamide (23A) A solution of cyclopropanecarbonyl chloride (0.54 g, 5.21 mmol) in DCM (10 mL) was added dropwise to an ice-cold solution of <strong>[374537-99-2]5-bromo-1H-indol-7-amine</strong> (1.0 g, 4.74 mmol) and triethylamine (0.991 mL, 7.11 mmol) in DCM (20 mL), and the mixture was stirred for 2 h. The reaction mixture was concentrated in vacuo and partitioned between ethyl acetate and water. Separated organic layer was dried over sodium sulphate and filtered, and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography using 20% ethyl acetate in hexanes to afford the title compound (1.1 g, 76%) as a red solid. 1H NMR (300 MHz, DMSO-d6): δ 11.0 (s, 1H), 10.08 (s, 1H), 7.72 (s, 1H), 7.48 (s, 1H), 7.41 (t, J=3.0 Hz, 1H), 6.43 (t, J=2.4 Hz, 1H), 1.90-1.86 (m, 1H), 0.88-0.82 (m, 4H). ESI-MS m/z=279 (M+H)+. |
76% | With triethylamine; In dichloromethane; for 2.0h;Cooling with ice; | A solution of cyclopropanecarbonyl chloride (0.54 g, 5.21 mmol) in DCM (10 mL) was added dropwise to an ice-cold solution of 5-bromo-lH-indol-7-amine (1.0 g, 4.74 mmol) and triethylamine (0.991 mL, 7.1 1 mmol) in DCM (20 mL), and the mixture was stirred for 2 h. The reaction mixture was concentrated in vacuo and partitioned between ethyl acetate and water. Separated organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography using 20% ethyl acetate in hexanes to afford the title compound (1.1 g, 76%) as a red solid. H NMR (300 MHz, DMSO- d6): δ 1 1.0 (s, 1H), 10.08 (s, 1H), 7.72 (s, 1H), 7.48 (s, 1H), 7.41 (t, J= 3.0 Hz, 1H), 6.43 (t, J= 2.4 Hz, 1H), 1.90 - 1.86 (m, 1H), 0.88 - 0.82 (m, 4H). ESI-MS m/z = 279 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 3h; | To 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)- 1,2,3,6- tetrahydropyridine hydrochloride 52 (0.7 g, 2.85 mmol) in acetonitrile (15 mL) was added cyclopropanecarbonyl chloride 53 (0.3 g, 2.87 mmol), followed by N,N-diisopropylethylamine (0.8 mL). The reaction mixture was stirred at room temperature for 3 hours, then passed through a silica gel column (eluting with ethyl acetate and hexanes) to provide crude product in light-colored fractions. The fractions were combined and concentrated. The residue was triturated with a mixture of ethyl acetate and hexanes. The mother liquid was collected and concentrated to provide compound 54 as an orange gel. The compound 54 was used for the subsequent reactions without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | Step 1. To a mixture of 3,5-difluorobenzene-l,2-diamine (1.0 g, 6.94 mmol) in dichloromethane (15 mL) was added cyclopropanecarbonyl chloride (726 mg, 6.94 mmol) dropwise at 0 C, then DIPEA (2.3 mL, 13.88 mmol). The reaction mixture was stirred at room temperature for 2 hours and the solvent was evaporated. To the residue in a microwave reaction vial was added acetonitrile (4 mL), then p-toluenesulfonic acid (cat. 10%). The reaction mixture was heated at 180 C for 30 minutes in a microwave oven, then partitioned between 10% MeOH:ethyl acetate and saturated NaHCC>3. The aqueous phase was extracted with ethyl acetate (2x) and the combined organic extract was washed with brine, dried over MgS04, then filtered and evaporated. The residue was separated by column chromatography, eluting with 0 - 10% dichloromethane :hexane to provide 2-cyclopropyl-5,7-difluoro-lH- benzo[d] imidazole (630.0 mg, 47%) as a brown solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | [0412] 1-(3-Chloro-4-fluorophenyl)ethan-1-one (1.5 g, 8.72 mmol, 1 eq) was dissolved in THF and cooled to -78 C. After 10 minutes of stirring, LHMDS (1 M in hexanes, 12.2 mL, 1.4 eq) was added dropwise over 20 minutes. This was allowed to stir for an additional 20 minutes then cyclopropanecarbonyl chloride (1.1 mL, 12.2 mmol, 1.4 eq) was added dropwise. The reaction was allowed to stir for 3 h at which time it was brought to room temperature. Reaction was quenched with 1 M HC1 and extracted with ethyl acetate. The aqueous layer was back extracted three times with ethyl acetate. The organic layer was washed with brine and dried over Mg504. The reaction mixture was purified by flash chromatography (Combi-flash Rf, hexane/ethyl acetate, 0-20% gradient) to give 1 -(3-chloro- 4-fluorophenyl)-3-cyclopropylpropane-1,3-dione (1 g, 50%). MS (ES) 241 (M+H) LCMS RT 1.357 mm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With pyridine; In 1,2-dichloro-ethane; at 20.0℃; for 16.0h;Reflux; | General procedure: Acid chloride (66.7 mmol) was added in one portion to asolution of the corresponding enamine 17, 21 (60.6 mmol) in 1,2-dichloroethane (200 mL) at RT. Pyridine (8.6 mL, 106 mmol) wasadded thereto also in one portion, and the mixture was stirred atreflux temperature for 16 h. The solvent was evaporated in vacuo,and the residue was partitioned between water (200 mL) and ethylacetate (200 mL). The organic layer was separated and washedsequentially with water (2150 mL), saturated aqueous NaHCO3(100 mL), and brine (100 mL), and dried (MgSO4). Evaporation ofthe extract in vacuo afforded crude compounds 18a-f, 22a-f asoils, which were used in the next step without purification.Analytical samples of the materials were purified by columnchromatography on silica gel eluting with ethyl acetate - hexane(1:3, v/v) mixture. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | 2-Amino-4-cyanopyridine (G1) (2.48 g, 20 mmol) was dissolved in dry DCM (240 mL), and a small portion of triethylamine was added to dissolve, and then potassium carbonate (14 g, 5 eq) was added. Stir at room temperature for 10 minutes and stir for 10 minutes in an ice bath. The cyclopropylcarbonyl chloride (5.6 mL, 3 eq) was dissolved in 15 mL of DCM, and the mixture was added dropwise with a sep. funnel, and then DMAP (200 mg, 0.1 eq) was added, and the mixture was allowed to react for 10 hours at room temperature for 16 hours. The reaction was completed by TLC. The potassium carbonate was filtered off with filter paper and celite, and the filter cake was washed with DCM, and the filtrate was directly dried to the next step. Pure product G2 was a white powder with a yield of 92%. | |
92% | <strong>[42182-27-4]2-amino-4-nitrylpyridine</strong> (6) (2.48 g, 20 mmol) was dissolved in dry DCM (240 mL),Add a small amount of triethylamine to help solubilize,Add potassium carbonate (14g, 5eq),Stir for 10 minutes at room temperature,Stir for 10 minutes in an ice bath.Dissolve cyclopropylformyl chloride (5.6mL, 3eq) in 15mL DCM,Add dropwise to the reaction solution with a separatory funnel,Finally, DMAP (200 mg, 0.1 eq) was added, and the reaction was performed at room temperature for 16 hours after 10 minutes in an ice bath.TLC monitors the completion of the reaction,Use filter paper and diatomaceous earth to filter out potassium carbonate,DCM washed filter cake,The filtrate was spin-dried directly for the next reaction.Pure product 2 was a white powder with a yield of 92%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With dmap; In dichloromethane; at 0 - 20℃;Inert atmosphere; | General procedure: Acyl chloride (0.18 mmol, 1.1 eq) was added at 0 C to a solution of <strong>[436-77-1]fangchinoline</strong> (100 mg, 0.16 mmol) and DMAP (0.032 mmol, 0.2eq) in 2 mL dry CH2Cl2 under argon and stirred for 2-4 h. The reaction mixture was quenched with a saturated aqueous solution of sodium bicarbonate and extracted three times with CH2Cl2. The combined organic phase was dried over anhydrous magnesium sulfate before vacuum suction filtration. The removal of the solventin vacuo afforded the crude product, which was chromatographied on silica gel (CH2Cl2/MeOH, 50/1 v/v, 0.1% TEA) to provide the pureproduct 1a-1e, 2a-2g, 3a-3e and 4a-4h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9%; 0.8% | To 3-oxocyclohexane-l-carbonitrile [17983-30-1] (63 mg, 0.49 mmol) and 2-cyano-N- (cyclopropylmethyl)acetamide [114153-25-2] (79 mg, 0.55 mmol) in THF (1 mL) was added ammonium acetate (52 mg, 0.675 mmol) and acetic acid (30 m). The reaction mixture was stirred at 70 C for 3 h. To the reaction mixture was added sulphur [7704-34-9] (26 mg, 0.81 mmol), EtOH (3 mL) and triethylamine (210 pL, 1.49 mmol) and the mixture was warmed at 65 C overnight and the mixture was concentrated in vacuo. To the residue was added EtOAc (5 mL) and 10% potassium bisulfate (2 mL), the organic layer was separated and washed with saturated sodium hydrogen carbonate solution followed by brine. The organic phase was separated, dried (Na2S04), filtered and concentrated in vacuo to yield a crude brown oil. To the residue was added DCM (2.5 mL) and DIPEA (130 pL, 0.75 mmol) and the mixture was cooled to 0 C in an ice-bath and a solution of (4293) cyclopropanecarbonyl chloride [4023-34-1] (75 mg, 0.70 mmol) in DCM (0.5 mL) was added. The reaction mixture was stirred at r.t. for 4 h before addition of saturated sodium hydrogen carbonate solution. The organic phase was separated with a phase separation cartridge and the aqueous was further extracted with DCM (2 mL). The combined organic layers were concentrated in vacuo to yield the crude products which were purified by preparative HPLC (basic), to afford title compound example 64 (15 mg, 9%). LCMS [M+H]+ 344.10, RT 4.11 minutes, (Methodl3). Preparative HPLC purification (acidic) of impure fractions from the initial purification (basic) afforded title compound example 65 (1.4 mg, 0.8%). LCMS [M+H]+ 344.10, [M+Na]+ 366.13, RT 4.60 minutes, 100.0% purity (Method 21). LCMS [M+H]+ 344.10, [M+Na]+ 366.08, [M-H] 342.06, RT 4.30 minutes, 97.08% purity (Method 13). |
Tags: 4023-34-1 synthesis path| 4023-34-1 SDS| 4023-34-1 COA| 4023-34-1 purity| 4023-34-1 application| 4023-34-1 NMR| 4023-34-1 COA| 4023-34-1 structure
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