Structure of 54287-92-2
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CAS No. : | 54287-92-2 |
Formula : | C8H10N2O2 |
M.W : | 166.18 |
SMILES Code : | O=C(OCC)NC1=CC=NC=C1 |
MDL No. : | MFCD00160359 |
InChI Key : | RPJQHJLOMYJUHA-UHFFFAOYSA-N |
Pubchem ID : | 766500 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P264-P280-P302+P352-P305+P351+P338-P332+P313-P337+P313-P362 |
* 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 |
---|---|---|
90% | With triethylamine; In dichloromethane; at 0 - 20℃; | To a solution of 4-aminopyridine (20.0 g, 212 mmol) in CH2Cl2 (200 mL) at 0C was added triethylamine (30.0 mL, 212 mmol) and ethyl chloroformate (20.3 mL, 212 mmol). The resulting mixture was allowed to warm to rt overnight then was concentrated. The solid products were slurried with saturated aqueous NaHCO3, stirred for 1 h, concentrated and dried under vacuum. The crude product was slurried with hot MeOH (500 mL) for 1 h, filtered and the filtrate was concentrated. The crude carbamate was recrystallized from toluene/hexanes to give 31.8 g (90% yield) of pure ethyl carbamate. |
89% | With triethylamine; In dichloromethane; at -8℃; for 5.0h;Large scale; | Triethylamine (1295.23 g, 12.75 mol) and ethyl chloroformate (1153.12 g, 10.63 mol) were added to a solution of 4-aminopyridine(1000.06 g, 10.62 mol) in anhydrous DCM (1.2 L) at -8 C over 2 h. The resulting mixture was stirred at -8 C for 3 h. The reaction mixture was adjusted to pH 5-6 by 5% hydrochloric acid. Then the aqueous phase was extracted with DCM (3 × 1 L). The DCM phases were combined, dried over MgSO4 and concentrated to afford 4 as: White solid; yield 1574.64 g (89%); m.p. 126.7-127.4 C (lit. 25 127-128 C); 1H NMR (600 MHz, CDCl3): δ 8.72 (s, 1H), 8.46 (d, J = 5.1 Hz, 2H), 7.45 (d, J = 5.1 Hz, 2H), 4.25 (q, J = 6.9 Hz, 2H), 1.31 (t, J = 7.0 Hz, 3H); 13C NMR (150 MHz, CDCl3): δ 153.4, 150.1, 146.3, 112.7, 61.6, 14.4; HRMS (ESI) for C8H10N2O2: [M + H]+: calcd: 167.0821; found: 167.0821. |
In pyridine; | PREPARATIVE EXAMPLE 2 4-ETHOXYCARBONYLAMINOPYRIDINE STR36 4-Aminopyridine (17.34 grams) (184.3) is dissolved in dry pyridine (217 ml.) and cooled to 0 C. over 30 minutes. Ethyl chloroformate (17.2 ml.) (180.7 mmoles) is added and the solution is stirred at 0 C. for 1 hour and then at 25 C. for 40 hours. The mixture is diluted with CH2 Cl2 and washed with saturated aqueous NaHCO3 and water. The CH2 Cl2 is dried (MgSO4), filtered and evaporated to dryness. The residue is chromatographed on silica gel using 2%(10% saturated NH4 OH in MeOH)--CH2 Cl2 to give the title compound (Yield: 10 grams, 33%, M+ |
In pyridine; | PREPARATIVE EXAMPLE 4 4-ETHOXYCARBONYLAMINOPYRIDINE STR54 4-Aminopyridine (17.34 grams) (184.3) was dissolved in dry pyridine (217 ml.) and cooled to 0 C. over 30 minutes. Ethyl chloroformate (17.2 ml.) (180.7 mmoles) was added and the solution was stirred at 0 C. for 1 hour and then at 25 C. for 40 hours. The mixture was diluted with CH2 Cl2 and washed with saturated aqueous NaHCO3 and water. The CH2 Cl2 was dried (MgSO4), filtered and evaporated to dryness. The residue was chromatographed on silica gel using 2% (10% saturated NH4 OH in MeOH)--CH2 Cl2 to give the title compound (Yield: 10 grams, 33%, M+ 166). By using essentially the same procedure, with the exception that STR55 was used instead of 4-aminopyridine, the compound STR56 was obtained, respectively. | |
In pyridine; | PREPARATIVE EXAMPLE 2 4-ETHOXYCARBONYLAMINOPYRIDINE 4-Aminopyridine (17.34 grams) (184.3) is dissolved in dry pyridine (217 ml.) and cooled to 0C over 30 minutes. Ethyl chloroformate (17.2 ml.) (180.7 mmoles) is added and the solution is stirred at 0C for 1 hour and then at 25C for 40 hours. The mixture is diluted with CH2Cl2 and washed with saturated aqueous NaHCO3 and water. The CH2Cl2 is dried (MgSO4), filtered and evaporated to dryness. The residue is chromatographed on silica gel using 2%(10% saturated NH4OH in MeOH)-CH2Cl2 to give the title compound (Yield: 10 grams, 33%, M+ 166). By using essentially the same procedure, with the exception that is used instead of 4-aminopyridine, the compound is obtained, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In pyridine; | PREPARATIVE EXAMPLE 4 4-ETHOXYCARBONYLAMINOPYRIDINE STR39 4-Aminopyridine (17.34 grams) (184.3) was dissolved in dry pyridine (217 ml.) and cooled to 0 C. over 30 minutes. Ethyl chloroformate (17.2 ml.) (180.7 mmoles) was added and the solution was stirred at 0 C. for 1 hour and then at 25 C. for 40 hours. The mixture was diluted with CH2 Cl2 and washed with saturated aqueous NaHCO3 and water. The CH2 Cl2 was dried (MgSO4), filtered and evaporated to dryness. The residue was chromatographed on silica gel using 2% (10% saturated NH4 OH in MeOH)--CH2 Cl2 to give the product compound (Yield: 10 grams, 33%, M+ | |
In pyridine; | PREPARATIVE EXAMPLE 12 4-Ethoxycarbonylaminopyridine STR118 4-Aminopyridine (17.34 grams) (184.3) was dissolved in dry pyridine (217 ml.) and cooled to 0 C. over 30 minutes. Ethyl chloroformate (17.2 ml.) (180.7 mmoles) was added and the solution was stirred at 0 C. for 1 hour and then at 25 C. for 40 hours. The mixture was diluted with CH2 Cl2 and washed with saturated aqueous NaHCO3 and water. The CH2 Cl2 was dried (MgSO4), filtered and evaporated to dryness. The residue was chromatographed on silica gel using 2%(10% saturated NH4 OH in MeOH)-CH2 Cl2 to give the title compound (Yield: 10 grams, M+ 166). By using essentially the same procedure, with the exception that STR119 was used instead of 4-aminopyridine, the compound STR120 was obtained, respectively. | |
In pyridine; | PREPARATIVE EXAMPLE 12 4-ETHOXYCARBONYLAMINOPYRIDINE STR135 4-Aminopyridine (17.34 grams) (184.3) was dissolved in dry pyridine (217 ml.) and cooled to 0 C. over 30 minutes. Ethyl chloroformate (17.2 ml.) (180.7 mmoles) was added and the solution was stirred at 0 C. for 1 hour and then at 25 C. for 40 hours. The mixture was diluted with CH2 Cl2 and washed with saturated aqueous NaHCO3 and water. The CH2 Cl2 was dried (MgSO4), filtered and evaporated to dryness. The residue was chromatographed on silica gel using 2% (10% saturated NH4 OH in MeOH)--CH2 Cl2 to give the title compound (Yield: 10 grams, 33%, M+ 166). By using essentially the same procedure, with the exception that STR136 was used instead of 4-aminopyridine, the compound STR137 was obtained, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
19% | With 1-Methylpyrrolidine; In 1,4-dioxane; at 160℃; under 7500.75 Torr; for 6.0h;Autoclave; | Compound 4 (96.00 g, 577.83 mmol) was added to a solution of piperazine (59.65 g, 693.39 mmol) in 1,4-dioxane (400 mL) with 1-methylpyrrolidine (49.47 g, 581.44 mmol) as catalyst. The mixture was placed in an autoclave for 6 h with a pressure of 1 MPa, temperature of 160 C and a rotation speed of 385 r min-1. The solid that precipitated from the solution was purified by recrystallisation from methanol to give compound 2: Yield 35.92 g (19%); m.p.220.1-221.6 C; 1H NMR (600 MHz, DMSO-d6): δ 9.04 (s, 2H), 8.32 (d, J = 4.5 Hz, 4H), 7.49 (d, J = 4.8 Hz, 4H), 3.53 (s, 8H); 13C NMR (150MHz, DMSO-d6): δ 154.1, 149.8, 147.4, 113.0, 43.6; HRMS (ESI) for C16H18N6O2: [M + H]+: calcd: 327.1569; found: 327.1570 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With 1-Methylpyrrolidine; In 1,4-dioxane; at 160℃; under 7500.75 Torr; for 6.0h;Autoclave; Sealed tube; | Compound 4 (96.60 g, 581.44 mmol) was added to a solution of piperazine (258.42 g, 2907.17 mmol) in 1,4-dioxane (400 mL) with 1-methylpyrrolidine (49.47 g, 581.44 mmol) as catalyst. The mixture was placed in an autoclave for 6 h with a pressure of 1 MPa, temperature of 160 C and a rotation speed of 385 r min-1 and then concentrated. The residue was purified by column chromatography(ethyl acetate-methanol 5:1, v/v) to afford compound 5 (61.65 g, 50% yield). The product 5 was converted to the hydrochloride 1 and precipitated from the ethyl acetate (500 mL) after 36% hydrochloric acid (75 mL) was added dropwise. The mixture was filtered off and dried to obtain compound 1 (93% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | With 1-Methylpyrrolidine; In 1,4-dioxane; at 160℃; under 7500.75 Torr; for 6.0h;Autoclave; | Compound 4 (100.38 g, 604.19 mmol) was added to a solution of N-Boc-piperazine (154.10 g, 725.03 mmol) in 1,4-dioxane (400 mL)with 1-methylpyrrolidine (51.41 g, 604.19 mmol) as catalyst. The mixture was placed in an autoclave for 6 h with a pressure of 1 MPa, temperature of 160 C, rotation speed of 385 r min-1 and then the reaction mixture was concentrated. The residue was purified by column chromatography (dichloromethane-methanol 10:1, v/v). The residue was slurried with acetone and water (1:5, v/v) and then the mixture was filtered off and dried to afford compound 6 (31.62 g, 17% yield). The solid product 6 was dissolved in ethyl acetate (350 mL) and then 36% hydrochloric acid (30 mL) was added and the mixture stirred for 30 min. The product 6 was converted to the hydrochloride 1 in 91% yield. |
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