Structure of 722550-01-8
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CAS No. : | 722550-01-8 |
Formula : | C9H13N3 |
M.W : | 163.22 |
SMILES Code : | NC1=NC=CC(N2CCCC2)=C1 |
MDL No. : | MFCD08062967 |
InChI Key : | RKWAPJTWMVCWIE-UHFFFAOYSA-N |
Pubchem ID : | 21934587 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
at 205℃; for 0.5h;Microwave; | The 2-amino-4-pyrrolidin-l-ylpyridine used as a starting material was prepared as follows :-A mixture of 2-amino-4-chloropyridine (1 g) and pyrrolidine (2.59 ml) was heated to205C in a microwave oven for 30 minutes. The reaction mixture was purified by column chromatography on silica using a 10: 1 mixture of methylene chloride and a 3M methanolic ammonia solution as eluent. There was thus obtained the required starting material (1.05 g);1H NMR: (CDCl3) 2.0 (m, 4H), 3.28 (m, 4H), 4.49 (br s, 2H), 5.56 (m, IH), 5.95 (m, IH), 7.69(d, IH); Mass Spectrum: M+If" 164. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47.2% | To a stirred solution of (4,S)-7-(2-methylpyridin-4-yl)-2,3,4,5-tetrahydro-l,4- methanopyrido[2,3-£][l,4]diazepine (300 mg, 1.189 mmol in THF (30 mL) ) were added triethylamine (0.829 mL, 5.94 mmol) and triphosgene (353 mg, 1.189 mmol) under nitrogen, stirred at RT for 1 h. To this 4-(pyrrolidin-l-yl)pyridin-2-amine (388 mg, 2.378 mmol) was added and stirred at 70 C for 16 h. (TLC eluent: 10% MeOH in DCM, 1^:0.4, UV active). The reaction mixture was cooled to rt, partitioned between water and ethyl acetate (3X30 mL). The combined organic layer was washed with brine solution, dried over anhydrous Na2SC"4, filtered and filtrate was evaporated to get crude compound. The crude compound was purified by flash column chromatography (using neutral alumina and eluted at 20% EtOAc in pet ether) to afford the desired product (4,S)-7-(2-methylpyridin-4- yl)-N-(4-(pyrrolidin-l-yl)pyridin-2-yl)-3,4-dihydro-l,4-methanopyrido[2,3- £][l,4]diazepine-5(2H)-carboxamide (251 mg, 0.561 mmol, 47.2 % yield) as an off white solid. LCMS (m/z): 442.3 [M+H]+, Rt = 4.78 min.1H NMR (400 MHz, CDC13): delta 13.27 (s, 1 H), 8.60 (d, J = 5.3 Hz, 1 H), 8.28 (s, 1 H), 8.00 (d, J = 5.9 Hz, 1 H), 7.72 (dd, J = 5.5, 1.8 Hz, 1 H), 7.59 (d, J = 7.9 Hz, 1 H), 7.50 - 7.38 (m, 2 H), 6.19 (dd, J = 5.9, 2.3 Hz, 1 H), 5.70 (dd, J = 6.0, 3.2 Hz, 1 H), 3.39 (q, J = 6.2, 4.8 Hz, 3 H), 3.26 (s, 1 H), 3.27 - 3.12 (m, 3 H), 3.00 (dd, J = 12.0, 3.3 Hz, 1 H), 2.74 (s, 3 H), 2.32 (dddd, J = 14.0, 10.0, 6.2, 4.2 Hz, 1 H), 2.15 - 1.97 (m, 5 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | In acetone; at 75℃; for 16h; | A solution of 2-bromo-1-(5-chloro-2,4-dimethoxyphenyl)ethanone 3 (70 mg, 0.24 mmol) and <strong>[722550-01-8]4-(pyrrolidin-1-yl)pyridin-2-amine</strong> 4a (39 mg, 0.24 mmol) in acetone (3 mL) was heated at 75 C for 16 h. The reaction mixture was cooled to room temperature; the white precipitate was collected by filtration, washed with acetone, and dried under reduced pressure to afford 2-(5-chloro-2,4-dimethoxyphenyl)-7-(pyrrolidin-1-yl)imidazo[1 ,2-a]pyridine hydrobromide 5a (45 mg, 43%) as a pink solid. 1H NMR (300 MHz, DMSO-d6) . delta 13.03 (s, 1H), 8.50 (d, J = 7.6 Hz, 1H). 8.20 (s, 1H), 7.89 (s, 1H), 6.97 (s, 1H), 6.95 (dd, J=2.2, 7.6 Hz, 1H), 6.30 (d, J= 2.0 Hz, 1H), 4.05 (s, 3H), 3.99 (s, 3H). 3.48-3.38 (m, 4H), 2.08- 1.98 (m, 4H); HPLC ( Method 4) 98.7% (AUG), tR = 19.02 min. APCI MS m/z 358 [M + H]+ . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | In acetone; at 75℃; for 16h; | A solution of 2-bromo-1-(5-bromo-2,4-dimethoxyphenyl)ethanone 7 (124 rng, 0.367 mmol) and <strong>[722550-01-8]4-(pyrrolidin-1-yl)pyridin-2-amine</strong> 8 (60 mg, 0.367 mmol) in acetone (4 mL) was heated at 75 C for 16 h. The reaction mixture was cooled to room temperature; the white precipitate was collected by filtration and solid was washed with acetone. The solid was suspended in aqueous ammonia solution (10 ml.) and stirred for 2 h. The free base was collected by filtration and solid was washed with water, dried under reduced pressure to yield 2-(5-bromo-2,4-dimethoxyphenyl)-7-(pyrrolidin-1-yl)imidazo[1,2-a]pyridine 9a (51 mg, 35%) as an off-white solid. 1H NMR (300 MHz, CDCl3): delta 8.55 (s, 1H), 7.83 (d, J = 7.4 Hz, 1H), 7,80 (s, 1H), 6.55 (s, 1H), 6,43 (d, J = 2.2 Hz, 1H), 6.33 (dd, J = 2,2, 7,4 Hz, 1H), 3 ,99 (s, 3H), 3 ,94 (s, 3H), 3.40-3,30 (m, 4H), 2.10-2.00 (m, 4H); HPLC (Method 2) >99% (AUC), tR= 19.12 min: APCI MS m/z 404 [M + H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 80℃; | General procedure: 2,4-Dimethoxy-5-[7-(pyrrolidin-1-yl)imidazo|1,2-a]pyridin-2-yl]benzonitrile 63a was prepared in the same manner as 2-(5-bromo-2,4-dimethoxyphenyl)-7-(pyrrolidin-1-yl)imidazo[1,2-a]pyridine 9a and was obtained as an off-white solid (62% yield). The resulting compound was treated with HBr to obtain the desired hydrobroniide salt. 1H NMR (400 MHz, DMSO-d6): delta 8.49 (d. J= 7,4 Hz, 1H), 8.23 (s, IH), 8, 14 (s, IH), 7.00 (s, IH), 6.97-6.91 (m, III), 6,31 (s, I H), 4.12 (s, 3H), 4.04 (s, 3H), 3.44 (s, 4H), 2.03 (s, 4H). HPLC (Method 2) 97.12% (AUC), = 18.09 rnm. ESI MS m/z 349 [M + H | +. A solution of 2-bromo-1-(5-bromo-2,4-dimethoxyphenyl)ethanone 7 (124 rng, 0.367 mmol) and <strong>[722550-01-8]4-(pyrrolidin-1-yl)pyridin-2-amine</strong> 8 (60 mg, 0.367 mmol) in acetone (4 mL) was heated at 75 C for 16 h. The reaction mixture was cooled to room temperature; the white precipitate was collected by filtration and solid was washed with acetone. The solid was suspended in aqueous ammonia solution (10 ml.) and stirred for 2 h. The free base was collected by filtration and solid was washed with water, dried under reduced pressure to yield 2-(5-bromo-2,4-dimethoxyphenyl)-7-(pyrrolidin-1-yl)imidazo[1,2-a]pyridine 9a (51 mg, 35%) as an off-white solid. 1H NMR (300 MHz, CDCl3): delta 8.55 (s, 1H), 7.83 (d, J = 7.4 Hz, 1H), 7,80 (s, 1H), 6.55 (s, 1H), 6,43 (d, J = 2.2 Hz, 1H), 6.33 (dd, J = 2,2, 7,4 Hz, 1H), 3 ,99 (s, 3H), 3 ,94 (s, 3H), 3.40-3,30 (m, 4H), 2.10-2.00 (m, 4H); HPLC (Method 2) >99% (AUC), tR= 19.12 min: APCI MS m/z 404 [M + H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | In acetone; at 75℃; for 16h; | General procedure: 2-(5-Bromo-2-isopropoxy-4~methoxyphenyl)-7-(pyrrolidin"l-yl)imidazo| l,2-o]~ pyridine hydrobromide 73 was prepared in the same manner as 2-(5-bromo-2,4-dimethoxy- phenyl)"7-(pyrro3idin~l~yl)imidazo[l,2-a]pyridine 9a and was obtained as an off-white solid (26% yield). 1H NMR. (400 MHz, DMSO-c 6): delta 13.04 (s, IH), 8.61 (d, J= 7.6 Hz, IH), 8.11 (s, IH), 8.02 (s, IH), 6.95 (s, H), 6.93 (s, IH), 6.27 (s, IH), 5.06-4.97 (m, IH), 3,94 (s, 3H), 3,48-3.40 (m, 4H), 2.06-1.99 (rn, 4H), 1.44 (s, 3H), 1.42 (s, 31 1 }: HPLC (Method 3) >99% (AUC), fR = 18.93 min; ESI MS m/z 4?()| M + H]+ . A solution of 2-bromo-1-(5-bromo-2,4-dimethoxyphenyl)ethanone 7 (124 rng, 0.367 mmol) and <strong>[722550-01-8]4-(pyrrolidin-1-yl)pyridin-2-amine</strong> 8 (60 mg, 0.367 mmol) in acetone (4 mL) was heated at 75 C for 16 h. The reaction mixture was cooled to room temperature; the white precipitate was collected by filtration and solid was washed with acetone. The solid was suspended in aqueous ammonia solution (10 ml.) and stirred for 2 h. The free base was collected by filtration and solid was washed with water, dried under reduced pressure to yield 2-(5-bromo-2,4-dimethoxyphenyl)-7-(pyrrolidin-1-yl)imidazo[1,2-a]pyridine 9a (51 mg, 35%) as an off-white solid. 1H NMR (300 MHz, CDCl3): delta 8.55 (s, 1H), 7.83 (d, J = 7.4 Hz, 1H), 7,80 (s, 1H), 6.55 (s, 1H), 6,43 (d, J = 2.2 Hz, 1H), 6.33 (dd, J = 2,2, 7,4 Hz, 1H), 3 ,99 (s, 3H), 3 ,94 (s, 3H), 3.40-3,30 (m, 4H), 2.10-2.00 (m, 4H); HPLC (Method 2) >99% (AUC), tR= 19.12 min: APCI MS m/z 404 [M + H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 80℃; | General procedure: Compound 2-(4,5-dichloro-2-methoxyphenyl)-7-(pyrrolidin-1-yl)imidazo[1,2-a]pyridine 88 was prepared in the same manner as 2-(5-chloro-2,4-dimethoxyphenyl)-7-(pyrrolidin-1-yl)imidazo[1,2-a]pyridine 5a. The resulting hydrobromic acid salt was neutralized with dilute aqueous ammonia to obtain free base and as an off-white solid (48 rng, 72%). 1H NMR (400 MHz, CDC13): delta 8.48 (s. 1H), 7.87 (s, 1H), 7.85 (d, J = 7.6 Hz, 1H), 7.02 (s, 1H ), 6.42 (br s, 1H), 6,36 (dd, 1H, J= 2.4 Hz, 7.5), 3.97 (s, 3H), 3,38-3.33 (m, 4H), 2.07-2.03 (m, 4H); HPLC (Method 1) 99,73% (AUC), tR = 1 1,76 min.; APCI MS m/z 362 [ M + H ]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With silver carbonate; In 1,4-dioxane; at 100℃; for 12h;Schlenk technique; Inert atmosphere; | In the Schlenk reaction tube,Join7-(Pyrrolidin-1-yl)-2-aminopyridine163mg,273mg of silver carbonate, the system is replaced by nitrogen protection,Add 10 ml of 1,4-dioxane, 1-bromomethyl-phenylacetylene, 96 mg,The reaction was carried out at 100C for 12 hours. The reaction was stopped, the reaction system was filtered using celite, the filter residue was washed with 20-30 ml of dichloromethane, and the filtrates were combined.Elution with a gradient of ethyl acetate: petroleum ether = 1:8 to 8:1,Obtaining intermediates2-(4-bromomethylphenyl)-7-(pyrrolidin-1-yl)imidazo[1,2-a]pyridine122 mg, yield 69%. |
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