Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 18437-58-6 | MDL No. : | MFCD00186509 |
Formula : | C6H8N2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | GNCLPNMQEGMNTG-UHFFFAOYSA-N |
M.W : | 108.14 | Pubchem ID : | 728670 |
Synonyms : |
|
Num. heavy atoms : | 8 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.17 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 33.61 |
TPSA : | 38.91 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.67 cm/s |
Log Po/w (iLOGP) : | 1.15 |
Log Po/w (XLOGP3) : | 0.41 |
Log Po/w (WLOGP) : | 0.98 |
Log Po/w (MLOGP) : | 0.13 |
Log Po/w (SILICOS-IT) : | 1.14 |
Consensus Log Po/w : | 0.76 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.32 |
Solubility : | 5.13 mg/ml ; 0.0474 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.79 |
Solubility : | 17.4 mg/ml ; 0.161 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.99 |
Solubility : | 1.11 mg/ml ; 0.0103 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.06 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338-P310 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | at 70℃; for 3 h; | [2-METHYL-4-NITROPYRIDINE-N-OXIDE] (5 g, 32.4 mmol) and iron powder [(18. 1 G,] 324 mmol) in [ACOH] (300 mL) was mechanically stirred at [70° C FOR] 3h. The reaction mixture was cooled to room temperature and concentrated under vacuum. The pH of the residue was adjusted to pH [GT;] 10, by addition ofNaOH and a minimal amount-of water. The reaction mixture was taken up in a liquid-liquid extractor and extracted with CHC13 for 12 hours. The layers were separated, dried [(NA2S04)] and concentrated under vacuum to afford desired 4-amino-2-methylpyridine (3.5 g, >99percent yield). |
88% | for 24 h; | (3) 2-Methyl-4-nitropyridine-N-oxide (30 g) is dissolved in 330 ml of acetic acid.. The solution is treated under catalytic hydrogenation conditions under pressure with Parr in the presence of 20 g of 10 percent Pd/C (wet), and, 24-hour later, bubbled with nitrogen for 30 minutes followed by removal of Pd/C by filtration.. The filtrate is concentrated to remove acetic acid and the residue is combined with aqueous saturated potassium hydrogen carbonate solution to make the mixture basic.. After addition of tetrahydrofuran, the mixture is vigorously stirred and insoluble substances are removed by filtration.. The organic layer is separated and the aqueous layer is extracted with tetrahydrofuran (x2).. The combined organic layer is then concentrated in vacuo.. To the residue is added toluene, and the mixture is subjected to azeotropic evaporation to remove water to obtain precipitated solids.. The solids are dissolved in dichloromethane, and the solution is dried over magnesium sulfate and concentrated under reduced pressure.. The precipitated crystals are triturated with diisopropyl ether and collected by filtration.. The resultant crystals are air dried at 50 °C overnight to give 4-amino-2-methylpyridine (yield 18.7 g, 88 percent). Mp. 86-88 °C |
83% | at 80℃; for 2 h; | A solution OF 2-METHYL-4-NITROPYRIDINE-N-OXIDE (3.80 g, 24.6 mmol) in 100 ML of acetic acid was slowly heated with iron powder (6.89 g, 124 mmol) in a large flask (caution: the reaction becomes very exothermic upon turning brown). The resulting slurry was heated for 2 hours at 80 C. Excess acetic acid was removed IN VACUO, THE residue was taken up in 20percent aqueous sodium hydroxide solution, and 100 mL of chloroform (CHC13) was added and the mixture filtered through CELITES FILTER aid. The aqueous phase was extracted with two 200 mL portions of chloroform. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude product (2.2 g, 83percent yield) was used without further purification. A solution OF KI (1. 96 g, 11. 9 mmol) and 12 (1.87 g, 7.36 mmol) in 10 ML of water was added to a REFLUXING solution of the 2-methylpyridin-4-ylamine (1.00 g, 9.25 mmol) and sodium carbonate (683 mg, 6.44 mmol) in 5 ML of water. The mixture was heated at reflux for 2 hours, cooled to room temperature, and treated with 20 mL of ethyl acetate (EtOAc). Phases were separated and the aqueous layer was extracted with three 20 ML portions of ethyl acetate. The combined organic layers were washed with a saturated aqueous sodium thiosulfate (NA2S203) solution, dried over magnesium sulfate, and concentrated ILL vacuo. Flash chromatography (30percent ethyl acetate in hexanes to 100percent ethyl acetate, gradient) of the resulting residue yielded 4-amino-3-iodo-6-methylpyridine (first eluting: 226 mg, 11percent yield) and 4- AMINO-3-IODO-2-METHYLPYRIDINE (second eluting : 116 mg; 5percent yield). |
72% | Stage #1: at 20 - 100℃; for 2 h; |
4-Amino-2-methylpyridine (152)A stirred solution of 4-nitro-2-methylpyridine-iV-oxide (20 g, 0.13 mol) in AcOH (300 mL) is treated with iron powder (40 g, 0.72 mol) in one portion at RT. This grey suspension is then gently heated to 100°C and stirred 2 h. The reaction mixture is then filtered through celite, and the solids collected washed with acetonitrile (1 L). The dark brown filtrate is then reduced in vacuo, diluted with 6 M NaOH (500 mL) and extracted into TBME (4 x 200 mL). The TBME phases are combined, dried (MgSO4) and reduced in vacuo to afford the title compound. Yield: 10. I g (72percent). LC/MS tr 0.52 min. MS(ES+) m/z 216 (2M+H). |
72% | Stage #1: at 20 - 100℃; for 2 h; Stage #2: With sodium hydroxide In water |
Synthesis of Compound 3554-Amino-2-methylpyridine (152)A stirred solution of 4-nitro-2-methylpyridine-λ'-oxide (20 g, 0.13 mol) in AcOH (300 mL) was treated with iron powder (40 g, 0.72 mol) in one portion at RT. This grey suspension was then gently heated to 10O0C and stirred 2 h. The reaction mixture was then filtered through celite, and the solids collected washed with acetonitrile (1 L). The dark brown filtrate was then reduced in vacuo, diluted with 6 M NaOH (500 mL) and extracted into TBME (4 x 200 mL). The TBME phases were combined, dried (MgSO4) and reduced in vacuo to afford the title compound. Yield: 10.1 g (72percent). LC/MS tx 0.52 min. MS(ES+) m/z 216 (2M+H). |
72% | Stage #1: at 20 - 100℃; for 2 h; |
4-Amino-2-methylpyridine (152); A stirred solution of 4-nitro-2-methylpyridine-N-oxide (20 g, 0.13 mol) in AcOH (300 mL) is treated with iron powder (40 g, 0.72 mol) in one portion at RT. This grey suspension is then gently heated to 100°C and stirred 2 h. The reaction mixture is then filtered through celite, and the solids collected washed with acetonitrile (1 L). The dark brown filtrate is then reduced in vacuo, diluted with 6 M NaOH (500 mL) and extracted into TBME (4 x 200 mL). The TBME phases are combined, dried (MgSO4) and reduced in vacuo to afford the title compound. Yield: 10.1 g (72percent). LC/MS tt 0.52 min. MS(ES+) m/z 216 (2M+H). |
72% | Stage #1: at 20 - 100℃; for 2 h; Stage #2: With sodium hydroxide In water; acetonitrile |
Synthesis of Compound 355; 4-Amino-2-methylpyridine (152); A stirred solution of 4-nitro-2-methylpyridine-N-oxide (20 g, 0.13 mol) in AcOH(300 mL) is treated with iron powder (40 g, 0.72 mol) in one portion at RT. This grey suspension is then gently heated to 100°C and stirred 2 h. The reaction mixture is then filtered through celite, and the solids collected washed with acetonitrile (1 L).The dark brown filtrate is then reduced in vacuo, diluted with 6 M NaOH (500 mL) and extracted into TBME (4 x 200 mL). The TBME phases are combined, dried(MgSO4) and reduced in vacuo to afford the title compound. Yield: 10.1 g (72percent).LC/MS U 0.52 min.MS(ES+) m/z 216 (2M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63.2% | With nitric acid; sodium nitrite In water at -17 - 0℃; | [0220] To a solution of 2-methylpyridin-4-amine (10.2 g, 94 mmol) and nitric acid (56.5 ml, 1273 mmol) in water (75 mL) was added a solution of sodium nitrite (9.44 g, 137 mmol) inowater (38 mL) at 0 C with vigorous stirring over 25 minutes. The reaction was then stirred oat 0 C for 30 minutes and stored in refrigerator set at -17°C overnight. The reaction mixture was filtered and the solids dried under vacuum to give 2- methylpyridin-4-ol (6.5 g, 59.6 mmol, 63.2 percent yield) as beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.53 - 2.60 (m, 3 H) 7.01 - 7.17 (m, 2 H) 8.36 - 8.49 (m, 1 H). MS [M+H] found 110.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: With hydrogen bromide; sodium nitrite In water at -10 - 20℃; for 16.5 h; |
4-Bromo-2-methylpyridine (153)A stirred solution of amino-pyridine 152 (10.1 g, 93.4 mmol) in 48percent aqueous HBr (165 mL) at -10"C is treated with a pre-cooled (0°C) solution of sodium nitrite (7.04 g, 0.102 mol) in water (165 mL) dropwise over 0.5 h. The solution is then warmed to RT and stirred 16 h. It is then diluted with 4 M NaOH (400 mL) and extracted into TBME (4 x 150 mL). The TBME phases are combined, dried (MgSO4) and reduced in vacuo to afford the title compound. Yield: 14.8 g (92percent). LC/MS tτ 0.57 min. MS(ES+) m/z 174, 172 (M+H). |
92% | With hydrogen bromide; sodium nitrite In water at -10 - 20℃; for 16.5 h; | 4-Bromo-2-methylpyridine (153)A stirred solution of amino-pyridine 152 (10.1 g, 93.4 mmol) in 48percent aqueous HBr (165 mL) at -10°C was treated with a pre-cooled (0°C) solution of sodium nitrite <n="205"/>(7.04 g, 0.102 mol) in water (165 mL) dropwise over 0.5 h. The solution was then warmed to RT and stirred 16 h. It was then diluted with 4 M NaOH (400 mL) and extracted into TBME (4 x 150 mL). The TBME phases were combined, dried(MgSO4) and reduced in vacuo to afford the title compound.Yield: 14.8 g (92percent).LC/MS tr 0.57 rain.MS(ES+) m/z 174, 172 (M+H). |
92% | Stage #1: With hydrogen bromide; sodium nitrite In water at -10 - 20℃; for 16.5 h; |
4-Bromo-2-methylpyridine (153); A stirred solution of amino-pyridine 152 (10.1 g, 93.4 mmol) in 48percent aqueous HBr (165 mL) at -10°C is treated with a pre-cooled (0°C) solution of sodium nitrite (7.04 g, 0.102 mol) in water (165 mL) dropwise over 0.5 h. The solution is then warmed to RT and stirred 16 h. It is then diluted with 4 M NaOH (400 mL) and extracted into TBME (4 x 150 mL). The TBME phases are combined, dried (MgSO4) and reduced in vacuo to afford the title compound. Yield: 14.8 g (92percent). LC/MS U 0.57 min. MS(ES+) m/z 174, 172 (M+H). |
92% | Stage #1: With hydrogen bromide; sodium nitrite In water at 0 - 20℃; for 16.5 h; Stage #2: With sodium hydroxide In water |
4-Bromo-2-methylpyridine (153); A stirred solution of amino-pyridine 152 (10.1 g, 93.4 mmol) in 48percent aqueous HBr(165 mL) at -10°C is treated with a pre-cooled (0°C) solution of sodium nitrite (7.04 g, 0.102 mol) in water (165 mL) dropwise over 0.5 h. The solution is then warmed toRT and stirred 16 h. It is then diluted with 4 M NaOH (400 mL) and extracted into TBME (4 x 150 mL). The TBME phases are combined, dried (MgSO4) and reduced in vacuo to afford the title compound.Yield: 14.8 g (92percent).LC/MS /, 0.57 min.MS(ES+) m/z 174, 172 (M+H). |
89% | Stage #1: With hydrogen bromide; sodium nitrite In water at -15 - 15℃; Stage #2: With copper(I) bromide In water at -15 - 20℃; for 12 h; |
-Methyl-4-aminopyridine (3. 86 g, 35.69 mmol) in [48percent] aqueous HBr (24 [ML)] was cooled to -15°C and [NAN02] (4.9 g, 71.4 mmol) in water (34 mL) was added slowly. (Note: The temperature was maintained between-10 to [15 °C] during the addition. ) CuBr [(510 MG,] 3.6 mmol) was added to the above reaction mixture at-15° C and slowly allowed to warm to room temperature over 12 hours. The pH of the reaction mixture was adjusted to [PH =10,] by addition [OF NAOH (11 G] in 21 mL water). The reaction mixture was filtered through celite and washed with ether/water. The layers were separated and the aqueous layer was extracted twice with ether. The combined organic extracts were dried [(NA2SO4),] concentrated under vacuum, and purified by silica gel chromatography (50percent ether in hexanes) to afford [4-BROMO-2-METHYLPYRIDINE] [(5.] 48 g, 89percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8% | With iodine; sodium carbonate; potassium iodide In water for 7 h; Reflux | 5-iodo-2-methylpyridin-4-amine (i55): To a solution of 2-methylpyridin-4-amine (5 g, 46 mmol) in water (25 ml_), Na2C03 (3.4 g, 32 mmol) was added and the reaction mixture was refluxed. Kl (9.8 g, 59 mmol) and l2 (9.3 g, 36 mmol in 50 mL water) were added and refluxed for 7h. The reaction mixture was quenched with sodium thiosulphate solution and the compound was extracted with DCM. The organic layer was separated dried over sodium sulphate and concentrated under reduced pressure. The residue obtained was purified by silica gel (100:200 mesh) column chromatography using 25percent ethyl acetate in hexane as eluent to afford desired product 5-iodo-2-methylpyridin-4-amine (i55) (0.85 g, Yield 8percent). 1H NMR (400 MHz, DMSO-d6): δ 2.20 (s, 3H), 6.00 (s, 2H), 6.49 (s, 1 H), 8.22 (s, 1 H). MS (ESI) m/e (M+1 )+: 235 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | With iodine; sodium carbonate; potassium iodide In water for 2 h; Heating / reflux | A solution OF 2-METHYL-4-NITROPYRIDINE-N-OXIDE (3.80 g, 24.6 mmol) in 100 ML of acetic acid was slowly heated with iron powder (6.89 g, 124 mmol) in a large flask (caution: the reaction becomes very exothermic upon turning brown). The resulting slurry was heated for 2 hours at 80 C. Excess acetic acid was removed IN VACUO, THE residue was taken up in 20percent aqueous sodium hydroxide solution, and 100 mL of chloroform (CHC13) was added and the mixture filtered through CELITES FILTER aid. The aqueous phase was extracted with two 200 mL portions of chloroform. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude product (2.2 g, 83percent yield) was used without further purification. A solution OF KI (1. 96 g, 11. 9 mmol) and 12 (1.87 g, 7.36 mmol) in 10 ML of water was added to a REFLUXING solution of the 2-methylpyridin-4-ylamine (1.00 g, 9.25 mmol) and sodium carbonate (683 mg, 6.44 mmol) in 5 ML of water. The mixture was heated at reflux for 2 hours, cooled to room temperature, and treated with 20 mL of ethyl acetate (EtOAc). Phases were separated and the aqueous layer was extracted with three 20 ML portions of ethyl acetate. The combined organic layers were washed with a saturated aqueous sodium thiosulfate (NA2S203) solution, dried over magnesium sulfate, and concentrated ILL vacuo. Flash chromatography (30percent ethyl acetate in hexanes to 100percent ethyl acetate, gradient) of the resulting residue yielded 4-amino-3-iodo-6-methylpyridine (first eluting: 226 mg, 11percent yield) and 4- AMINO-3-IODO-2-METHYLPYRIDINE (second eluting : 116 mg; 5percent yield). |