Structure of 444731-73-1
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CAS No. : | 444731-73-1 |
Formula : | C9H9N3O2 |
M.W : | 191.19 |
SMILES Code : | CN1N=C2C=C(C=CC2=C1C)[N+]([O-])=O |
MDL No. : | MFCD10703326 |
InChI Key : | JHGRUPGVUMAQQU-UHFFFAOYSA-N |
Pubchem ID : | 10465149 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 54.78 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.64 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.59 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.8 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.79 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.68 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.33 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.57 |
Solubility | 0.516 mg/ml ; 0.0027 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.76 |
Solubility | 0.336 mg/ml ; 0.00176 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.24 |
Solubility | 1.09 mg/ml ; 0.0057 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.19 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.85 |
* 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 |
---|---|---|
96% | With hydrogenchloride; tin(ll) chloride In diethylene glycol dimethyl ether; water at 0℃; for 0.583333 h; | To a stirred solution of 2, [3-DIMETHYL-6-NITRO-2H-INDAZOLE] (1.13 g) in 2- methoxyethyl ether (12 [ML),] at [0] [C,] was added a solution of 4.48 g of tin [(LL)] chloride in 8.9 ml of concentrated HCI dropwise over 5 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 40 ml of diethyl ether was added to reaction, resulting in precipitate formation. The resulting precipitate was isolated by filtration and washed with diethyl ether, and afforded a yellow solid (1.1 g, 95 [percent),] the HCI salt 2,3- [DIMETHYL-2H-INDAZOL-6-AMINE.APOS;H] NMR (300 MHz, [DMSO-D6)] 8 7. [77] (d, [J =] 8.9 [HZ,] [1 H),] 7.18 (s, [1 H),] 7.88 (m, [1 H),] 4.04 (s, 3H), 2.61 (s, 3H). MS [(ES+,] m/z) 162 (M+H). |
95% | With hydrogenchloride; tin(ll) chloride In diethylene glycol dimethyl ether; water at 0℃; for 0.583333 h; | To a stirred solution of 2,3-dimethyl-6-nitro-2H-indazole (1.13 g) in 2- methoxyethyl ether (12 ml), at 0 9C, was added a solution of 4.48 g of tin(ll) chloride in 8.9 ml of concentrated HCI dropwise over 5 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 40 ml of diethyl ether was added to reaction, resulting in precipitate formation. The resulting precipitate was isolated by filtration and washed with diethyl ether, and afforded a yellow solid (1.1 g, 95 percent), the HCI salt 2,3-dimethyl-2H-indazol- 6-amine. 1H NMR (300 MHz, DMSO-d6) δ 7.77 (d, J = 8.9 Hz, 1 H), 7.18 (s, 1H), 7.88 (m, 1 H), 4.04 (s, 3H), 2.61 (s, 3H). MS (ES+, m/z) 162 (M+H). |
95% | With tin(ll) chloride In diethylene glycol dimethyl ether; water at 0℃; for 0.583333 h; | To a stirred solution of 2,3-dimethyl-6-nitro-2H-indazole (1.13 g) in 2- methoxyethyl ether (12 ml), at 0 9C, was added a solution of 4.48 g of tin(ll) chloride in 8.9 ml of concentrated HCI dropwise over 5 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 40 ml of diethyl ether was added to reaction, resulting in precipitate formation. The resulting precipitate was isolated by filtration and washed with diethyl ether, and afforded a yellow solid (1.1 g, 95 percent), the HCI salt 2,3-dimethyl-2H-indazol- 6-amine. 1H NMR (300 MHz, DMSO-d6) δ 7.77 (d, J = 8.9 Hz, 1 H), 7.18 (s, 1 H), 7.88 (m, 1 H), 4.04 (s, 3H), 2.61 (s, 3H). MS (ES+, m/z) 162 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Trimethyl orthoformate (11 mmol, 1.17 g) was added over a 2 min period [TO A] solution of boron [TRIFLUORIDE] etherate (12.5 mmol, 1.77 g in methylene chloride (2.0 mL) which had been [COOLED TO-30 C.] The mixture was warmed to 0 [C] for 15 min and was then cooled to-70 [C.] The nitro [INDAZOLE] (10 mmol, 1.77 g) was slurried in methylene chloride (30 mL) and was added all at once to the cooled mixture. The mixture was stirred at-70 [C] for 15 min and at ambient temperature for 17 h. After 17 h the mixture was red and heterogeneous. The reaction mixture was quenched with saturated sodium bicarbonate solution (20 mL) and the organic layer separated. The aqueous layer was extracted with methylene chloride (30 mL). The methylene chloride layers were combined and extracted with water (30 mL). The methylene chloride layer was distilled under reduced pressure until-10 mL remained. Propanol (10 mL) was added and the remainder of the methylene chloride removed under reduced pressure, resulting in a yellow slurry. The product was isolated by filtration to give 2, 3-dimethyl-6-nitro-2H-indazole (65 percent, [7MMOL,] 1.25 g) as a light yellow [POWDER.APOS;H] NMR (300 MHz, [DMSO-D6)] 8 8.51 (s, [1 H),] 7.94 (d, [J =] 9.1 Hz, [1 H),] 7.73 [(D, J] = 8.9 Hz, [1 H),] 4.14 (s, [3H),] 2.67 (s, [3H).] MS (ES+, m/z) 192 (M+H). | |
65% | Procedure 2: Trimethyl orthoformate (11 mmol, 1.17 g) was added over a 2 min period to a solution of boron trifluoride etherate (12.5 mmol, 1.77 g in methylene chloride (2.0 mL) which had been cooled to -30° C. The mixture was warmed to 0° C. for 15 min and was then cooled to -70° C. The nitro indazole (10 mmol, 1.77 g) was slurried in methylene chloride (30 mL) and was added all at once to the cooled mixture. The mixture was stirred at -70° C. for 15 min and at ambient temperature for 17 h. After 17 h the mixture was red and heterogeneous. The reaction mixture was quenched with saturated sodium bicarbonate solution (20 mL) and the organic layer separated. The aqueous layer was extracted with methylene chloride (30 mL). The methylene chloride layers were combined and extracted with water (30 mL). The methylene chloride layer was distilled under reduced pressure until 10 mL remained. Propanol (10 mL) was added and the remainder of the methylene chloride removed under reduced pressure, resulting in a yellow slurry. The product was isolated by filtration to give 2,3-dimethyl-6-nitro-2H-indazole (65percent, 7 mmol, 1.25 g) as a light yellow powder. 1H NMR (300 MHz, DMSO-d6) delta 8.51 (s, 1H), 7.94 (d, J=9.1 Hz, 1H), 7.73 (d, J=8.9 Hz, 1H), 4.14 (s, 3H), 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H). | |
65% | Procedure 2: Trimethyl orthoformate (11 mmol, 1.17 g) was added over a 2 min period to a solution of boron trifluoride etherate (12.5 mmol, 1.77 g in methylene chloride (2.0 mL) which had been cooled to-30 °C. The mixture was warmed to 0 °C for 15 min and was then cooled to-70 °C. The nitro indazole (10 mmol, 1.77 g) was slurried in methylene chloride (30 mL) and was added all at once to the cooled mixture. The mixture was stirred at-70 °C for 15 min and at ambient temperature for 17 h. After 17 h the mixture was red and heterogeneous. The reaction mixture was quenched with saturated sodium bicarbonate solution (20 mL) and the organic layer separated. The aqueous layer was extracted with methylene chloride (30 mL). The methylene chloride layers were combined and extracted with water (30 mL). The methylene chloride layer was distilled under reduced pressure until - 10 mL remained. Propanol (10 mL) was added and the remainder of the methylene chloride removed under reduced pressure, resulting in a yellow slurry. The product was isolated by filtration to give 2,3-dimethyl-6-nitro-2H- indazole (65 percent, 7mmol, 1.25 g) as a light yellow powder. |
65% | With boron trifluoride diethyl etherate; In dichloromethane; at -70 - 20℃; for 17.5333h;Product distribution / selectivity; | Thmethyl orthoformate (1 1 mmol, 1 .17 g) was added over a 2 min period to a solution of boron trifluoride etherate (12.5 mmol, 1.77 g in methylene chloride (2.0 mL) which had been cooled to -30 0C. The mixture was warmed to 0 0C for 15 min and was then cooled to -70 0C. The nitro indazole (10 mmol, 1.77 g) was slurried in methylene chloride (30 mL) and was added all at once to the cooled mixture. The mixture was stirred at -70 0C for 15 min and at ambient temperature for 17 h. After 17 h the mixture was red and heterogeneous. The reaction mixture was quenched with saturated sodium bicarbonate solution (20 mL) and the organic layer separated. The aqueous layer was extracted with methylene chloride (30 mL). The methylene chloride layers were combined and extracted with water (30 mL). The methylene chloride layer was distilled under reduced pressure until ~ 10 mL remained. Propanol (10 mL) was added and the remainder of the methylene chloride removed under reduced pressure, resulting in a yellow slurry. The product was isolated by filtration to give 2,3-dimethyl-6- nitro-2H-indazole (65 percent, 7mmol, 1.25 g) as a light yellow powder. 1H NMR (300 MHz, DMSOd6) delta 8.51 (s, 1 H), 7.94 (d, J = 9.1 Hz, 1 H), 7.73 (d, J = 8.9 Hz, 1 H), 4.14 (s, 3H), 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H). |
1.77 g (0.0125 mol) of boron trifluoride etherate was added to the dichloromethane solution,The mixture was cooled to -30 ° C,1.17 g (0.011 mol) of trimethyl orthoformate were added over 2 minutes,The mixture was warmed to 0 ° C,After 15 minutes, the temperature was lowered to -70 ° C,A solution of 1.77 g (0.01 mol) of <strong>[6494-19-5]3-methyl-<strong>[6494-19-5]6-nitro-1H-indazole</strong></strong> in 30 ml of methylene chloride was added,Stirred for 15 minutes,The mixture was stirred at room temperature for 17 hours,20 ml of saturated sodium bicarbonate solution was added,Liquid separation,The aqueous layer was extracted with dichloromethane,The organic layers were combined,Vacuum distillation to retain about 10ml,10 ml of propanol was added,The residual methylene chloride was distilled off under reduced pressure,To give a yellow syrup,filter,To give 2,3-dimethyl-6-nitro-2H-indazole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.4% | In ethyl acetate; at 25 - 30℃; for 20h; | Example 1 Trimethyloxonium tetrafluoroborate (125.2 g, 0.85 mol) was added to a stirred suspension of <strong>[6494-19-5]3-methyl-6-nitro-indazole</strong> (100 g, 0.56 mol) in ethyl acetate (2000 mL) over a period of 4 hours in four equal lots at 1 hour time intervals. The reaction mixture was stirred at 25° C. to 30° C. for 16 hours. The solvent was recovered under reduced pressure. A saturated sodium bicarbonate solution (3240 mL) was added to the mixture slowly, and the reaction mixture was extracted with 4:1 mixture of dichloromethane isopropyl alcohol (1080 mL*5). The solvent was recovered under reduced pressure. Methyl tert-butyl ether (800 mL) was added to the residue, and the reaction mixture was stirred for 30 minutes at 45° C. to 50° C. The reaction mixture was cooled to 25° C. to 30° C. and was stirred at this temperature for 30 minutes. The solid was filtered, washed with methyl tert-butyl ether (100 mL*2), and dried in an air oven at 50° C. for 12 hours to afford 2,3-dimethyl-6-nitro-2H-indazole as a yellow solid. Yield: 82.4percent w/w |
73% | In acetone; at 20℃; for 3h;Product distribution / selectivity; | To a stirred solution of 18.5 g (0.11 mol) of 3-methyl-6-nitro-7H-indazole in 350 ml acetone, at room temperature, was added 20 g (0.14 mol) of trimethyloxonium tetraflouroborate. After the solution was allowed to stir under argon for 3 hours, the solvent was removed under reduced pressure. To the resulting solid was added <n="26"/>saturated aqueous NaHCO3 (600 mL) and a 4:1 mixture of chloroform-isopropanol (200 ml), the mixture was agitated and the layers were separated. The aqueous phase was washed with additional chloroform: isopropanol (4 x 200 mL) and the combined organic phase was dried (Na2SO4). Filtration and removal of solvent gave a tan solid. The solid was washed with ether (200 mL) to afford 2,3-dimethyl-6-nitro- 2tf-indazole as a yellow solid (15.85 g, 73 percent). 1H NMR (300 MHz, DMSO-d6) delta 8.51 (s, 1H), 7.94 (d, J = 9.1 Hz, 1 H), 7.73 (d, J = 8.9 Hz, 1 H), 4.14 (s, 3H), 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H). |
73% | In acetone; at 20℃; for 3h; | To a stirred solution of 18.5 g (0.11 mol) of [3-METHYL-6-NITRO-1H-INDAZOLE] in 350 ml acetone, at room temperature, was added 20 g (0.14 mol) of [TRIMETHYLOXONIUM] [TETRAFLOUROBORATE.] After the solution was allowed to stir under argon for 3 hours, the solvent was removed under reduced pressure. To the resulting solid was added saturated aqueous [NAHC03] (600 mL) and a 4: 1 mixture of chloroform-isopropanol (200 [ML),] the mixture was agitated and the layers were separated. The aqueous phase was washed with additional chloroform: isopropanol (4 x 200 mL) and the combined organic phase was dried [(NA2S04).] Filtration and removal of solvent gave a tan solid. The solid was washed with ether (200 mL) to afford 2, 3-dimethyl-6-nitro-2H-indazole as a yellow solid (15.85 [G,] 73 [percent).APOS;H] NMR (300 MHz, [DMSO-D6)] 8 8.51 (s, [1 H),] 7.94 (d, [J= 9.] 1 Hz, [1 H),] 7.73 (d, [J =] 8.9 Hz, [1 H),] 4.14 (s, 3H), 2.67 (s, 3H). MS [(ES+,] [M/Z)] 192 (M+H). |
73% | In acetone; at 20℃; for 3h;Product distribution / selectivity; | To a stirred solution of 18.5 g (0.11 mol) of 3-methyl-6-nitro- 7H-indazole in 350 ml acetone, at room temperature, was added 20 g (0.14 mol) of trimethyloxonium tetraflouroborate. After the solution was allowed to stir under argon for 3 hours, the solvent was removed under reduced pressure. To the resulting solid was added saturated aqueous NaHCO3 (600 ml_) and a 4:1 mixture of chloroform-isopropanol (200 ml), the mixture was agitated and the layers were separated. The aqueous phase was washed with additional chloroform: isopropanol (4 x 200 mL) and the combined organic phase was dried (Na2SO4). Filtration and removal of solvent gave a tan solid. The solid was washed with ether (200 mL) to afford 2,3-dimethyl-6-nitro-2H-indazole as a yellow solid (15.85 g, 73 percent). 1H NMR (300 MHz, DMSO-d6) delta 8.51 (s, 1 H), 7.94 (d, J = 9.1 Hz, 1 H), 7.73 (d, J = 8.9 Hz, 1 H), 4.14 (s, 3H)1 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H). |
73% | In acetone; at 20℃; for 3h;Inert atmosphere; | Intermediate Example 11 Preparation of 2,3-dimethyl-2H-indazol-6-amine To a stirred solution of 18.5 g (0.11 mol) of <strong>[6494-19-5]3-methyl-<strong>[6494-19-5]6-nitro-1H-indazole</strong></strong> in 350 ml acetone, at room temperature, was added 20 g (0.14 mol) of trimethyloxonium tetraflouroborate. After the solution was allowed to stir under argon for 3 hours, the solvent was removed under reduced pressure. To the resulting solid was added saturated aqueous NaHCO3 (600 ml) and a 4:1 mixture of chloroform-isopropanol (200 ml), and the mixture was agitated and the layers were separated. The aqueous phase was washed with additional chloroform: isopropanol (4 x 200 ml) and the combined organic phase was dried (Na2SO4). Filtration and removal of solvent gave a tan solid. The solid was washed with ether (200 ml) to afford 2,3-dimethyl-6-nitro-2H-indazole as a yellow solid (15.85 g, 73 percent). 1H NMR (300 MHz, d6DMSO) delta 8.51 (s, 1H), 7.94 (d, J = 9.1 Hz, 1H), 7.73 (d, J = 8.9 Hz, 1H), 4.14 (s, 3H), 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H).; To a stirred solution of 2,3-dimethyl-6-nitro-2H-indazole (1.13 g) in 2-methoxyethyl ether (12 ml), at 0 °C, was added a solution of 4.48 g of tin(II) chloride in 8.9 ml of concentrated HCl dropwise over 5 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 40 ml of diethyl ether was added to reaction, resulting in precipitate formation. The resulting precipitate was isolated by filtration and washed with diethyl ether, and afforded a yellow solid (1.1 g, 95 percent), the HCl salt 2,3-dimethyl-2H-indazol-6-amine. 1H NMR (300 MHz, d6DMSO) delta 7.77 (d, J = 8.9 Hz, 1H), 7.18 (s, 1H), 7.88 (m, 1H), 4.04 (s, 3H), 2.61 (s, 3H). MS (ES+, m/z) 162 (M+H). |
73% | In acetone; at 20℃; for 3h;Inert atmosphere; | 18.5 g (0.11 mol) of <strong>[6494-19-5]3-methyl-<strong>[6494-19-5]6-nitro-1H-indazole</strong></strong> was dissolved in 350 ml of acetone,20 g (0.14 mol) of trimethyloxonium tetrafluoroborate was added with stirring at room temperature,The reaction solution was filled with argon for 3 h,The solvent was removed under reduced pressure,The solid was added with 600 ml of aqueous NaHCO3 solution,200 ml of a mixture of chloroform and isopropanol (4: 1)The organic phase was dried over anhydrous sodium sulfate,filter,The solvent was distilled off,To give a brown solid,Washed with ether,15.85 g of 2,3-dimethyl-6-nitro-2H-indazole was obtained in a yield of 73percent. |
73% | Intermediate Example 1 Preparation of 2,3-dimethyl-6-nitro-2H-indazole Procedure 1: To a stirred solution of 18.5 g (0.11 mol) of <strong>[6494-19-5]3-methyl-<strong>[6494-19-5]6-nitro-1H-indazole</strong></strong> in 350 ml acetone, at room temperature, was added 20 g (0.14 mol) of trimethyloxonium tetrafluoroborate. After the solution was allowed to stir under argon for 3 hours, the solvent was removed under reduced pressure. To the resulting solid was added saturated aqueous NaHCO3 (600 mL) and a 4:1 mixture of chloroform-isopropanol (200 ml), the mixture was agitated and the layers were separated. The aqueous phase was washed with additional chloroform: isopropanol (4*200 mL) and the combined organic phase was dried (Na2SO4). Filtration and removal of solvent gave a tan solid. The solid was washed with ether (200 mL) to afford 2,3-dimethyl-6-nitro-2H-indazole as a yellow solid (15.85 g, 73percent). 1H NMR (300 MHz, DMSO-d6) delta 8.51 (s, 1H), 7.94 (d, J=9.1 Hz, 1H), 7.73 (d, J=8.9 Hz, 1H), 4.14 (s, 3H), 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H). | |
73% | In acetone; at 20℃; for 3h;Product distribution / selectivity; | Intermediate Example 1 Preparation of 2,3-dimethyl-6-nitro-2H-indazole Procedure 1: To a stirred solution of 18.5 g (0.11 mol) of 3-methyl-6-nitro-1H- indazole in 350 ml acetone, at room temperature, was added 20 g (0.14 mol) of trimethyloxonium tetraflouroborate. After the solution was allowed to stir under argon for 3 hours, the solvent was removed under reduced pressure. To the resulting solid was added saturated aqueous NaHC03 (600 mL) and a 4: 1 mixture of chloroform-isopropanol (200 ml), the mixture was agitated and the layers were separated. The aqueous phase was washed with additional chloroform: isopropanol (4 x 200 mL) and the combined organic phase was dried (Na2S04). Filtration and removal of solvent gave a tan solid. The solid was washed with ether (200 mL) to afford 2,3-dimethyl-6-nitro-2H-indazole as a yellow solid (15.85 g, 73 percent). |
73% | In acetone; at 20℃; for 3h;Product distribution / selectivity; | To a stirred solution of 18.5 g (0.1 1 mol) of 3-methyl-6-nitro-7/-/-indazole in 350 ml acetone, at room temperature, was added 20 g (0.14 mol) of thmethyloxonium tetraflouroborate. After the solution was allowed to stir under argon for 3 hours, the solvent was removed under reduced pressure. To the resulting solid was added saturated aqueous NaHCO3 (600 ml_) and a 4:1 mixture of chloroform-isopropanol (200 ml), the mixture was agitated and the layers were separated. The aqueous phase was washed with additional chloroform: isopropanol (4 x 200 mL) and the combined organic phase was dried (Na2SO4). Filtration and removal of solvent gave a tan solid. The solid was washed with ether (200 mL) to afford 2,3-dimethyl-6-nitro-2/-/-indazole as a yellow solid (15.85 g, 73 percent). 1H NMR (300 MHz, DMSOd6) delta 8.51 (s, 1 H), 7.94 (d, J = 9.1 Hz, 1 H), 7.73 (d, J = 8.9 Hz, 1 H), 4.14 (s, 3H), 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H). |
32% | Example 50: Process for preparation of DMND[000167] To a stirred solution of 3-methyl-6-nitro- l H-indazole (MNID) (5.0 g, 28.2 mmol) in acetone (95 mL, 19V) at ambient temperature was added trimethyloxonium tetrafluoroborate (5.3 g, 35.8 mmol, 1 .27 eq). Stirring was continued under nitrogen and the reaction was monitored by TLC. After 5.5 h another 1 g of trimethyloxonium tetrafluoroborate was added to the reaction in an attempt to push it to completion. After 7.5 h total reaction time the solvent was removed and saturated sodium bicarbonate ( 162 mL) was added to the residue, followed by a 4: 1 mixture of CHC : IPA (54 mL). The resulting mixture was agitated and the layers were separated. The aqueous phase was washed with additional CHCI3: IPA 4: 1 (4x54 mL) and the combined organic phases were dried ( a2SO,)), filtered and evaporated to dryness. The resulting brown solid was washed with diethylether (about 160 mL) and dried on the filter under nitrogen/vacuum to afford crude DMND (3.2 g, 87.5percent purity). The crude material (2.9 g) was then dissolved in EtOH (50 mL) at reflux and the solution was gradually cooled to ambient temperature and then to 5 °C, and was kept at this temperature for 1 h. The resulting precipitate was isolated by filtration and the filter cake was washed with cold EtOH ( 10 mL) and dried in a vacuum oven (35 mbar) at 55°C for 4 h to give 2,3-dimethyl-6-nitro-2H-indazole ( 1 .57g, ca 32percent) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sulfuric acid; In dimethyl sulfoxide; at 50℃; for 72h;Product distribution / selectivity; | In a 25 ml round bottom flask <strong>[6494-19-5]3-methyl-6-nitroindazole</strong> (7.27 mmol, 1.28 g) was dissolved with stirring in DMSO (4.0 mL) and was treated with concentrated sulfuric acid (7.27 mmol, 0.73 g) to yield a thick slurry. The slurry was treated with dimethyl sulfate (21.1 mmol, 2.66 g). The mixture was heated under nitrogen at 50 0C for 72 h. After 72 h a thick yellow slurry was obtained. The slurry was cooled and was slowly treated with saturated sodium bicarbonate solution (10 mL). The mixture was <n="27"/>extracted with methylene chloride (2 x 20 ml_). The methylene chloride layers were combined and back extracted with water (20 mL). The methylene chloride layer was treated with propanol (10 mL) and the methylene chloride was removed by distillation under reduced pressure. The solid was isolated by filtration and the yellow solid washed with heptane (5 mL) and air-dried. The 2,3-dimethyl-6-nitro-2H-indazole product (70percent, 0.97 g) was obtained as a light yellow solid. 1H NMR (300 MHz, DMSO-d6) delta 8.51 (s, 1 H), 7.94 (d, J= 9.1 Hz, 1 H), 7.73 (d, J= 8.9 Hz, 1 H), 4.14 (s, 3H), 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H). |
70% | With sulfuric acid; In dimethyl sulfoxide; at 50℃; for 72h; | In a 25 ml round bottom flask <strong>[6494-19-5]3-methyl-6-nitroindazole</strong> (7.27 mmol, 1.28 g) was dissolved with stirring in DMSO (4.0 mL) and was treated with concentrated sulfuric acid (7.27 mmol, 0.73 g) to yield a thick slurry. The slurry was treated with dimethyl sulfate (21.1 [MMOL,] 2.66 g). The mixture was heated under nitrogen at 50 [C] for 72 h. After 72 h a thick yellow slurry was obtained. The slurry was cooled and was slowly treated with saturated sodium bicarbonate solution (10 mL). The mixture was extracted with methylene chloride (2 x 20 mL). The methylene chloride layers were combined and back extracted with water (20 mL). The methylene chloride layer was treated with propanol (10 mL) and the methylene chloride was removed by distillation under reduced pressure. The solid was isolated by filtration and the yellow solid washed with heptane (5 mL) and air-dried. The 2, 3-dimethyl-6-nitro-2H-indazole product (70percent, 0.97 g) was obtained as a light yellow [SOLID.APOS;H] NMR (300 MHz, DMSO- [D6)] [6 8.] 51 (s, [1 H),] 7.94 (d, [J=] 9.1 Hz, [1 H),] 7.73 (d, [J= 8.] 9 Hz, [1 H),] 4.14 (s, 3H), 2.67 (s, 3H). MS [(ES+,] m/z) 192 (M+H). |
70% | With sulfuric acid; In dimethyl sulfoxide; at 50℃; for 72h;Product distribution / selectivity; | In a 25 ml round bottom flask <strong>[6494-19-5]3-methyl-6-nitroindazole</strong> (7.27 mmol, 1.28 g) was dissolved with stirring in DMSO (4.0 mL) and was treated with concentrated sulfuric acid (7.27 mmol, 0.73 g) to yield a thick slurry. The slurry was treated with dimethyl sulfate (21.1 mmol, 2.66 g). The mixture was heated under nitrogen at 50 0C for 72 h. After 72 h a thick yellow slurry was obtained. The slurry was cooled and was slowly treated with saturated sodium bicarbonate solution (10 mL). The mixture was extracted with methylene chloride (2 x 20 mL). The methylene chloride layers were combined and back extracted with water (20 mL). The methylene chloride layer was treated with propanol (10 mL) and the methylene chloride was removed by distillation under reduced pressure. The solid was isolated by filtration and the yellow solid washed with heptane (5 mL) and air-dried. The 2,3-dimethyl-6-nitro-2H-indazole product (70percent, 0.97 g) was obtained as a light yellow solid. 1H NMR (300 MHz, DMSO-d6) delta 8.51 (s, 1 H), 7.94 (d, J = 9.1 Hz, 1 H), 7.73 (d, J= 8.9 Hz, 1 H), 4.14 (s, 3H), 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H). |
70% | With sulfuric acid; In dimethyl sulfoxide; at 50℃; for 72h;Inert atmosphere; | A solution of 1.28 g (0.00727 mol) of <strong>[6494-19-5]3-methyl-<strong>[6494-19-5]6-nitro-1H-indazole</strong></strong> was dissolved in 4 ml of DMSO,(0.00727 mol) of concentrated sulfuric acid to give a thick slurry,Further, 2.66 g (0.0211 mol) of dimethyl sulfate was added,The mixture was heated at 50 ° C under nitrogen for 72 hours,A thick yellow slurry was obtained,After cooling,10 ml of a saturated aqueous solution of sodium hydrogencarbonate was added slowly,Extracted twice with 20 ml of dichloromethane,The organic layers were combined,Reverse extraction with 20 ml of water,The methylene chloride layer was added with 10 ml of propanol,The methylene chloride was distilled off under reduced pressure,Filtration,To give a yellow solid,Washed with 5 ml of heptane,dry,To give 2,3-dimethyl-6-nitro-2H-indazole, 0.97 g, yield 70percent. |
70% | In a 25 ml round bottom flask <strong>[6494-19-5]3-methyl-6-nitroindazole</strong> (7.27 mmol, 1.28 g) was dissolved with stirring in DMSO (4.0 mL) and was treated with concentrated sulfuric acid (7.27 mmol, 0.73 g) to yield a thick slurry. The slurry was treated with dimethyl sulfate (21.1 mmol, 2.66 g). The mixture was heated under nitrogen at 50° C. for 72 h. After 72 h a thick yellow slurry was obtained. The slurry was cooled and was slowly treated with saturated sodium bicarbonate solution (10 mL). The mixture was extracted with methylene chloride (2.x.20 mL). The methylene chloride layers were combined and back extracted with water (20 mL). The methylene chloride layer was treated with propanol (10 mL) and the methylene chloride was removed by distillation under reduced pressure. The solid was isolated by filtration and the yellow solid washed with heptane (5 mL) and air-dried. The 2,3-dimethyl-6-nitro-2H-indazole product (70percent, 0.97 g) was obtained as a light yellow solid. 1H NMR (300 MHz, DMSO-d6) delta 8.51 (s, 1H), 7.94 (d, J=9.1 Hz, 1H), 7.73 (d, J=8.9 Hz, 1H), 4.14 (s, 3H), 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H). | |
70% | With sulfuric acid; In dimethyl sulfoxide; at 50℃; for 72h;Product distribution / selectivity; | Procedure 3: In a 25 ml round bottom flask <strong>[6494-19-5]3-methyl-6-nitroindazole</strong> (7.27 mmol, 1.28 g) was dissolved with stirring in DMSO (4.0 mL) and was treated with concentrated sulfuric acid (7.27 mmol, 0.73 g) to yield a thick slurry. The slurry was treated with dimethyl sulfate (21.1 mmol, 2.66 g). The mixture was heated under nitrogen at 50 °C for 72 h. After 72 h a thick yellow slurry was obtained. The slurry was cooled and was slowly treated with saturated sodium bicarbonate solution (10 mL). The mixture was extracted with methylene chloride (2 x 20 mL). The methylene chloride layers were combined and back extracted with water (20 mL). The methylene chloride layer was treated with propanol (10 mL) and the methylene chloride was removed by distillation under reduced pressure. The solid was isolated by filtration and the yellow solid washed with heptane (5 mL) and air-dried. The 2,3-dimethyl-6-nitro-2H-indazole product (70percent, 0.97 g) was obtained as a light yellow solid. |
70% | With sulfuric acid; In dimethyl sulfoxide; at 50℃; for 72h;Product distribution / selectivity; | In a 25 ml round bottom flask <strong>[6494-19-5]3-methyl-6-nitroindazole</strong> (7.27 mmol, 1.28 g) was dissolved with stirring in DMSO (4.0 mL) and was treated with concentrated sulfuric <n="30"/>acid (7.27 mmol, 0.73 g) to yield a thick slurry. The slurry was treated with dimethyl sulfate (21.1 mmol, 2.66 g). The mixture was heated under nitrogen at 50 0C for 72 h. After 72 h a thick yellow slurry was obtained. The slurry was cooled and was slowly treated with saturated sodium bicarbonate solution (10 ml_). The mixture was extracted with methylene chloride (2 x 20 ml_). The methylene chloride layers were combined and back extracted with water (20 ml_). The methylene chloride layer was treated with propanol (10 mL) and the methylene chloride was removed by distillation under reduced pressure. The solid was isolated by filtration and the yellow solid washed with heptane (5 mL) and air-dried. The 2,3-dimethyl-6-nitro-2/-/-indazole product (70percent, 0.97 g) was obtained as a light yellow solid. 1H NMR (300 MHz, DMSOd6) delta 8.51 (s, 1 H), 7.94 (d, J = 9.1 Hz, 1 H), 7.73 (d, J = 8.9 Hz, 1 H), 4.14 (s, 3H), 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Trimethyl orthoformate (11 mmol, 1.17 g) was added over a 2 min period to a solution of boron trifluoride etherate (12.5 mmol, 1.77 g in methylene chloride (2.0 mL) which had been cooled to -30 0C. The mixture was warmed to 0 0C for 15 min and was then cooled to -70 0C. The nitro indazole (10 mmol, 1.77 g) was slurried in methylene chloride (30 mL) and was added all at once to the cooled mixture. The mixture was stirred at -70 0C for 15 min and at ambient temperature for 17 h. After 17 h the mixture was red and heterogeneous. The reaction mixture was quenched with saturated sodium bicarbonate solution (20 mL) and the organic layer separated. The aqueous layer was extracted with methylene chloride (30 mL). The methylene chloride layers were combined and extracted with water (30 mL). The methylene chloride layer was distilled under reduced pressure until ~ 10 mL remained. Propanol (10 mL) was added and the remainder of the methylene chloride removed under reduced pressure, resulting in a yellow slurry. The product was isolated by filtration to give 2,3-dimethyl-6-nitro-2H-indazole (65 percent, 7mmol, 1.25 g) as a light yellow powder. 1H NMR (300 MHz, DMSO-d6) 58.51 (s, 1 H), 7.94 (d, J= 9.1 Hz, 1 H), 7.73 (d, J= 8.9 Hz, 1 H), 4.14 (s, 3H), 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With hydrogenchloride; tin(ll) chloride; In diethylene glycol dimethyl ether; water; at 0℃; for 0.583333h; | To a stirred solution of 2, [3-DIMETHYL-6-NITRO-2H-INDAZOLE] (1.13 g) in 2- methoxyethyl ether (12 [ML),] at [0] [C,] was added a solution of 4.48 g of tin [(LL)] chloride in 8.9 ml of concentrated HCI dropwise over 5 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 40 ml of diethyl ether was added to reaction, resulting in precipitate formation. The resulting precipitate was isolated by filtration and washed with diethyl ether, and afforded a yellow solid (1.1 g, 95 [%),] the HCI salt 2,3- [DIMETHYL-2H-INDAZOL-6-AMINE.'H] NMR (300 MHz, [DMSO-D6)] 8 7. [77] (d, [J =] 8.9 [HZ,] [1 H),] 7.18 (s, [1 H),] 7.88 (m, [1 H),] 4.04 (s, 3H), 2.61 (s, 3H). MS [(ES+,] m/z) 162 (M+H). |
95% | With hydrogenchloride; tin(ll) chloride; In diethylene glycol dimethyl ether; water; at 0℃; for 0.583333h; | To a stirred solution of 2,3-dimethyl-6-nitro-2H-indazole (1.13 g) in 2- methoxyethyl ether (12 ml), at 0 9C, was added a solution of 4.48 g of tin(ll) chloride in 8.9 ml of concentrated HCI dropwise over 5 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 40 ml of diethyl ether was added to reaction, resulting in precipitate formation. The resulting precipitate was isolated by filtration and washed with diethyl ether, and afforded a yellow solid (1.1 g, 95 %), the HCI salt 2,3-dimethyl-2H-indazol- 6-amine. 1H NMR (300 MHz, DMSO-d6) delta 7.77 (d, J = 8.9 Hz, 1 H), 7.18 (s, 1H), 7.88 (m, 1 H), 4.04 (s, 3H), 2.61 (s, 3H). MS (ES+, m/z) 162 (M+H). |
95% | With tin(ll) chloride;hydrogenchloride; In diethylene glycol dimethyl ether; water; at 0℃; for 0.583333h; | To a stirred solution of 2,3-dimethyl-6-nitro-2H-indazole (1.13 g) in 2- methoxyethyl ether (12 ml), at 0 9C, was added a solution of 4.48 g of tin(ll) chloride in 8.9 ml of concentrated HCI dropwise over 5 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 40 ml of diethyl ether was added to reaction, resulting in precipitate formation. The resulting precipitate was isolated by filtration and washed with diethyl ether, and afforded a yellow solid (1.1 g, 95 %), the HCI salt 2,3-dimethyl-2H-indazol- 6-amine. 1H NMR (300 MHz, DMSO-d6) delta 7.77 (d, J = 8.9 Hz, 1 H), 7.18 (s, 1 H), 7.88 (m, 1 H), 4.04 (s, 3H), 2.61 (s, 3H). MS (ES+, m/z) 162 (M+H). |
95% | With hydrogenchloride; tin(ll) chloride; In diethylene glycol dimethyl ether; water; at 0℃; for 0.583333h;Inert atmosphere; Cooling with ice; | Intermediate Example 11 Preparation of 2,3-dimethyl-2H-indazol-6-amine To a stirred solution of 18.5 g (0.11 mol) of 3-methyl-6-nitro-1H-indazole in 350 ml acetone, at room temperature, was added 20 g (0.14 mol) of trimethyloxonium tetraflouroborate. After the solution was allowed to stir under argon for 3 hours, the solvent was removed under reduced pressure. To the resulting solid was added saturated aqueous NaHCO3 (600 ml) and a 4:1 mixture of chloroform-isopropanol (200 ml), and the mixture was agitated and the layers were separated. The aqueous phase was washed with additional chloroform: isopropanol (4 x 200 ml) and the combined organic phase was dried (Na2SO4). Filtration and removal of solvent gave a tan solid. The solid was washed with ether (200 ml) to afford 2,3-dimethyl-6-nitro-2H-indazole as a yellow solid (15.85 g, 73 %). 1H NMR (300 MHz, d6DMSO) delta 8.51 (s, 1H), 7.94 (d, J = 9.1 Hz, 1H), 7.73 (d, J = 8.9 Hz, 1H), 4.14 (s, 3H), 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H).; To a stirred solution of 2,3-dimethyl-6-nitro-2H-indazole (1.13 g) in 2-methoxyethyl ether (12 ml), at 0 C, was added a solution of 4.48 g of tin(II) chloride in 8.9 ml of concentrated HCl dropwise over 5 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 40 ml of diethyl ether was added to reaction, resulting in precipitate formation. The resulting precipitate was isolated by filtration and washed with diethyl ether, and afforded a yellow solid (1.1 g, 95 %), the HCl salt 2,3-dimethyl-2H-indazol-6-amine. 1H NMR (300 MHz, d6DMSO) delta 7.77 (d, J = 8.9 Hz, 1H), 7.18 (s, 1H), 7.88 (m, 1H), 4.04 (s, 3H), 2.61 (s, 3H). MS (ES+, m/z) 162 (M+H). |
95% | With hydrogenchloride; tin(ll) chloride; In diethylene glycol dimethyl ether; water; at 0℃; for 0.583333h; | Intermediate Example 2 Preparation of 2,3-dimethyl-6-amino-2H-indazole Procedure 1: To a stirred solution of 2,3-dimethyl-6-nitro-2H-indazole (1.13 g) in 2-methoxyethyl ether (12 ml), at 0 C., was added a solution of 4.48 g of tin(II) chloride in 8.9 ml of concentrated HCl dropwise over 5 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 40 ml of diethyl ether was added to reaction, resulting in precipitate formation. The resulting precipitate was isolated by filtration and washed with diethyl ether, and afforded a yellow solid (1.1 g, 95%), the HCl salt 2,3-dimethyl-2H-indazol-6-amine. 1H NMR (300 MHz, DMSO-d6) delta 7.77 (d, J=8.9 Hz, 1H), 7.18 (s, 1H), 7.88 (m, 1H), 4.04 (s, 3H), 2.61 (s, 3H). MS (ES+, m/z) 162 (M+H). |
95% | With hydrogenchloride; tin(ll) chloride; In diethylene glycol dimethyl ether; water; at 0℃; for 0.583333h; | Intermediate Example 2 Preparation of 2,3-dimethyl-6-amino-2H-indazole Procedure 1: To a stirred solution of 2,3-dimethyl-6-nitro-2H-indazole (1.13 g) in 2- methoxyethyl ether (12 ml), at 0 C, was added a solution of 4.48 g of tin(II) chloride in 8.9 ml of concentrated HCI dropwise over 5 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 40 ml of diethyl ether was added to reaction, resulting in precipitate formation. The resulting precipitate was isolated by filtration and washed with diethyl ether, and afforded a yellow solid (1.1 g, 95 %), the HCI salt 2,3-dimethyl-2H-indazol-6-amine. |
95% | With hydrogenchloride; tin(ll) chloride; In diethylene glycol dimethyl ether; water; at 0℃; for 0.583333h; | To a stirred solution of 2,3-dimethyl-6-nitro-2/-/-indazole (1.13 g) in 2- methoxyethyl ether (12 ml), at 0 0C, was added a solution of 4.48 g of tin(ll) chloride in 8.9 ml of concentrated HCI dropwise over 5 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 40 ml of diethyl ether was added to reaction, resulting in precipitate formation. The resulting precipitate was isolated by filtration and washed with diethyl ether, and afforded a yellow solid (1.1 g, 95 %), the HCI salt 2,3-dimethyl-2H-indazol-6- amine. 1H NMR (300 MHz, DMSOd6) delta 7.77 (d, J = 8.9 Hz, 1 H), 7.18 (s, 1 H), 7.88 (m, 1 H), 4.04 (s, 3H), 2.61 (s, 3H). MS (ES+, m/z) 162 (M+H). |
95% | With hydrogenchloride; tin(ll) chloride; In ethanol; water; at 0℃; | After stirring and mixing a concentrated hydrochloric acid solution (80 mL) of stannous chloride (0.24 mol) at 0 C. with ethanol (150 mL)From Li E 10 into the third mixing valve 11, the flow rate of Li E 10 was 2.56 mL / min. At the same time, the second micro-reaction in step (2)The effluent 2,3-dimethyl-6-nitro-2H-indazole product (0.0216 mol) from the reactor 9 flows into the third mixing valve 11. Two stocksAfter fully mixed, it enters the third micro-reactor 12 in the second continuous micro-channel reaction device, reacts at room temperature, and the residence timeFor 7.6min, the second receiving device 13 collects the reaction effluent, the second receiving device 13 is a container for ethanol, the volume of ethanol1.5L, 2,3-dimethyl-2H-indazole-6-amine hydrochloride was precipitated, S was the product, and the yield was 95%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: Preparation of 2-methyl-6-nitro-2H-indazole (5d). To a stirred mixture of <strong>[6494-19-5]6-nitro-1H-indazole</strong> (1.0 g, 0.0061 mmol) in dichloromethane (25.0 mL) was added trifluoromethanesulfonic acid (0.54 mL, 0.0061 mmol), stirred for 5?10 min at 25?35 °C. To this mixture was added methyl 2,2,2,-trichlroacetimidate (2.69 g, 0.015 mmol) at room temperature. The reaction mixture was stirred at room temperature for 16?18 h under N2. After reaction completion, chilled saturated NaHCO3 solution was added. The aqueous and organic phases were separated. Aqueous phase was extracted with dichloromethane 10 mL. Combined organic layers were washed with DM water (2 × 10 mL). Organic layer was dried over anhydrous Na2SO4, filtered, and evaporated completely under vacuum to obtain 2-methyl-6-nitro-2H-indazole (1.03 g, 95.0percent) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.1% | <strong>[6494-19-5]3-methyl-<strong>[6494-19-5]6-nitro-1H-indazole</strong></strong> (1a, 10.00 g, 56 mmol) and triethylenediamine (DABCO, 6.40 g, 56 mmol) were dissolved in 100 mL of DMF. The mixture was stirred for 15 min at room temperature, then dimethyl carbonate (DMC) (6.04 g, 67 mmol) was added dropwise to it. After the addition, the reaction mixture was heated to reflux and stirred for 6 h. After cooling to room temperature, 120 mL of water was added and stirred for 15 min, a large amount of light-yellow solid appeared, the solid was filtered and dried to give 2a (8.66 g, 81.1percent yield). Mp: 187~187.6 C. 1HNMR (400MHz, DMSO-d6) delta: 2.67 (s, 3H), 4.14 (s, 3H), 7.73 (d, J=9.2 Hz, 1H), 7.93 (d, J=8.8 Hz, 1H), 8.51 (s, 1H). | |
70.6% | With 1,4-diaza-bicyclo[2.2.2]octane; In N,N-dimethyl-formamide; isopropyl alcohol; at 70℃; for 20h; | In a 250 ml three-necked flask,40 ml of DMF was added,5 ml of isopropanol,17.7 g (0.1 mol) of <strong>[6494-19-5]3-methyl-<strong>[6494-19-5]6-nitro-1H-indazole</strong></strong>,Stirring dissolved,Further, 18 g (0.2 mol) of dimethyl carbonate was added,12.3 g (0.11 mol) of triethylenediamine.The reaction was heated to 70 ° C for 20 h,To room temperature,Poured into 900ml of ice water,Stirring 30mins,A large amount of yellow solid precipitated,Filtration,Dried in vacuo to give 13.5 g of a yellow solid,Yield 70.6percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.6% | Sodium (3.2g, 0.14mol) was addedportionwise to refluxingisopropanol (140ml)and stirred until the whole solution, was added 2-2 (13.0g, 0.073mol), plus complete reflux wascontinued for 3h. Iodomethane (30.0g,0.21mol) in isopropanol (45 ml of) the solution was refluxed for 5h. Cooled, allowed to stand overnight. Andfiltered to give a pale yellow solid 12.0g, yield 87.6percent. |
Tags: 444731-73-1 synthesis path| 444731-73-1 SDS| 444731-73-1 COA| 444731-73-1 purity| 444731-73-1 application| 444731-73-1 NMR| 444731-73-1 COA| 444731-73-1 structure
A235049 [1588440-92-9]
2,3-Dimethyl-5-nitro-2H-indazole
Similarity: 1.00
A235049 [1588440-92-9]
2,3-Dimethyl-5-nitro-2H-indazole
Similarity: 1.00
A298459 [444731-72-0]
2,3-Dimethyl-2H-indazol-6-amine
Similarity: 0.84
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P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
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 |
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