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Structure of 1824-81-3
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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. : | 1824-81-3 |
Formula : | C6H8N2 |
M.W : | 108.14 |
SMILES Code : | CC1=CC=CC(N)=N1 |
MDL No. : | MFCD00006331 |
InChI Key : | QUXLCYFNVNNRBE-UHFFFAOYSA-N |
Pubchem ID : | 15765 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H310-H301-H315-H319 |
Precautionary Statements: | P262-P264-P280-P337+P313-P301+P310+P330-P302+P352+P310 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅱ |
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 ? Topological Polar Surface Area: Calculated from |
38.91 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.26 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.44 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.98 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.54 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.14 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.87 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.34 |
Solubility | 4.91 mg/ml ; 0.0454 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.82 |
Solubility | 16.2 mg/ml ; 0.15 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.99 |
Solubility | 1.11 mg/ml ; 0.0103 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) |
No |
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 |
-6.65 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 |
0.0 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) |
1.18 |
* 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% | for 3 h; Reflux | To the solution of benzylisothiocyanate (83.0 g, 509.3 mmol) in acetone (700mL) was added compound 6-methylpyridin-2 -amine (50 g, 463.0mmol) in acetone (600 ml) dropwise, then the reaction mixture was stirred at reflux for 3h. The reaction mixture was poured on to crushed ice, then filtered and washed with water, water/MeOH (1 : 1) and MeOH to give l-benzoyl-3-(6- methylpyridin-2-yl)thiourea as a yellow solid (100.1 g, yield 80percent). To a solution of 1-benzoyl-3-(6-methylpyridin-2-yl)thiourea (60 g,221.4 mmol) in THF ( 1000 ml) was added 2N NaOH (243.5ml), then heated at reflux for 3 h. Cooled to RT and filtered to give (6-methylpyridin-2- yl)thiourea as a white solid (34.1 g, yield 92percent). A mixture of (6-methylpyridin-2-yl)thiourea (13.2 g, 79.16 mmol) and 2-bromo-l-(4-bromophenyl)ethan-l-one (22 g, 79.16 mmol) in ethanol (300 mL) was stirred at reflux for 3h, then concentrated and purified with silica gel column to give N-[4-(4-bromophenyl)-l,3-thiazol-2-yl]-6-methylpyridin-2-amine as a yellow solid (14.3 g,53percent). A solution of N-[4-(4-bromophenyl)-l,3-thiazol-2-yl]-6-methylpyridin-2-amine (5 g. 14.5mmol), Bis(pinacolato)diboron (4.8 g, 18.8mmol), Pd(dppf)2Ci2 (1.2 mg, 1.5mmol) and AcOK (4.3 g, 43.3mmol) in dioxane (100ml) was heated to 80 under 2 overnight. The mixture was evaporated to give (6-methyl-N-{4-[4-(tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl]-l,3-thiazol-2-yl}pyridin-2-amine). Coupling (200mg) with 2-dimethylamino-4- bromopyridine under standard conditions gave 33 mg from 200 mg of, yellow solid, 17 percent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With sulfuric acid; iodine; acetic acid; periodic acid In water at 80℃; for 6 h; | To a stirred solution of 6-methyl-pyridin-2-ylamine (30g, 278mmol, 1 eq) in acetic acid (167ml_) was added periodic acid (12.7g, 55.6mmol, 0.2eq) followed by addition of sulphuric acid (4.8ml_, 90.8mmol, 0.34eq), water (33ml_) and iodine (28.7g, 1 1 1 mmol, 0.4eq) at room temperature. Resulting reaction mixture was heated at 80°C for 6 hours. After complete consumption of starting material, reaction mixture was cooled and poured into sodium thiosulfate solution (200ml_), reddish oil was settled down at the bottom. Reaction mixture was decanted from reddish oil, and filtrate was basified with 50percent sodium hydroxide solution (100ml_), yellow colored solid was formed. Resulting solid was extracted with diethyl ether (2 x 200ml_) and dried over sodium sulfate. Organic layer was concentrated under reduced pressure to afford brown semi solid (60g, crude). Crude was purified by column chromatography using silica gel (100-200 mesh). Desired compound was eluted at 15percent EtOAc in hexane to get title compound as faint brown solid (50g, 77percent). H NMR (400 MHz, CDCI3)8: 2.52 (s, 3H), 4.43(bs, 2H), 6.09 (d, J = 8.4 Hz, 1 H), 7.65 (d, J = 8.44 Hz, 1 H). LC-MS (m/z): 235.3 (M+H). |
38% | With sulfuric acid; iodine; acetic acid In water | PREPARATION 2 2-amino-5-iodo-6-picoline A mixture of 2-amino-6-picoline (5.40 g), periodic acid (2.28 g), and iodine (5.00 g) is heated in a solution of acetic acid (30 mL), water (6 mL), and sulfuric acid (0.9 mL) at 80° C. for 3 h. The reaction is cooled to room temperature and poured into 100 mL 10percent aqueous sodium bisulfite. The aqueous solution is extracted with diethyl ether (3*100 mL). The combined organics are washed with 10percent NaOH, then dried over Na2SO4, filtered, and concentrated. Purification by chromatography (eluent EtOAc) affords a yellow liquid. The liquid is further dried on the vacuum pump where it crystallizes to afford 2-amino-5-iodo-6-picoline (4.48 g, 38percent). Physical characteristics are as follows: 1H NMR (300 MHz, DMSO-d6) δ 7.60, 6.09, 6.05, 2.38. |
7.5 g | With N-iodo-succinimide In N,N-dimethyl-formamide at 20℃; | (A) 5-iodo-6-methylpyridin-2-amine (0307) To a solution of 6-methylpyridin-2-amine (10 g, 0.092 mol) in DMF (50 mL) was added N-iodosuccinimide (15 g, 0.13 mol), and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with water (200 mL), and the precipitated solid was collected by filtration and washed with ethyl acetate to give the title compound (7.5 g). MS: [M+H]+ 235.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A mixture of 2-amino-6-methylpyridine (10.00 g, 92.47 mmol), ethyl 4-chloro- acetoacetate (16.24 mL, 120.2 mmol), and polyphosphoric acid (50.00 g) was stirred at 125 0C. After 5.5 h, the mixture was removed from the heat. To the cooled mixture was added ice-water (200 mL) and neutralized with 2 N NaOH (400 mL) to pH 6-7. The resulting precipitate was collected by filtration, washed with water (~ 400 mL), and dried to give 2-(chloromethyl)-6-methyl-4H-pyrido- [l,2-a]pyrimidin-4-one as a dark brown solid: 1H NMR (400 MHz, DMSO-d6) delta ppm 7.68 (1 H, dd, J=9.0, 7.0 Hz), 7.40 (1 H, dd, J=9.0, 0.8 Hz), 6.93 (1 H, d, J=6.7 Hz), 6.36 (1 H, s), 4.58 (2 H, s), 2.93 (3 H, s); Mass Spectrum (ESI) m/e = 208.9 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 18 By reacting 2-amino-6-methyl-pyridine with 3-carbomethoxy-4-hydroxy-2-methyl-thieno[2,3-e]-1,2-thiazine 1,1-dioxide for 7 hours in a manner analogous to that described in Example 1, there is obtained 4-hydroxy-2-methyl-N-(6-methyl-2-pyridyl)-2H-thieno[2,3-e]-1,2-thiazine-3-carboxamide 1,1-dioxide of decomposition point 216-218 C (recrystallisation from benzene). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-chloro-succinimide; In hexane; N,N-dimethyl-formamide; | 2-Amino-5-chloro-6-methylpyridine (45) To a stirred solution of 2-amino-6-methylpyridine (10.80 g, 100.0 mmol) in dry DMF (50 mL) was added dropwise a solution of NCS (13.35 g, 100.0 mmol) in dry DMF (60 mL) at 0 C. over 20 min. The resulting brown yellow solution was stirred at 0 C. for 1 h, and at room temperature for 3 h, then poured into ice-water (about 300 mL). The resulting mixture was extracted with EtOAc (4*100 mL). The extracts were combined, washed with brine (6*50 mL), dried (MgSO4), and rota-evaporated. To the residual viscous black oil was added hexane (200 mL) and it was heated to boiling with stirring. The hot hexane solution was decanted carefully, concentrated to about 60 ml, then allowed to stand at room temperature overnight. The resulting crystals were filtered and dried at room temperature in vacuo, giving 6.06 g (42%) of 45 as orange-colored long needles, mp 74-5 C. (lit. 73-4 C., Cress et al., J. Org. Chem. 93-6 (1976)). 1 H NMR (CDCl3) delta2.439 (s, 3H), 4.376 (bs, 2H), 6.302 (d, 1H, J=8.5), 7.340 (d, 1H, J=8.5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25.9% | With ferrous(II) sulfate heptahydrate; sulfuric acid; boric acid; In water; glycerol; at 0 - 135℃; for 4h; | Sodium-3-nitrobenzenesulfonate (17.5 g, 77.7 mmol), boric acid (2.4 g, 38.8 mmol), and ferrous sulfate heptahydrate (1.4 g, 0.5 mmol) were added to 23.1 mL of 98percent sulfuric acid. After cooling to 0 °C, glycerol (12.5 mL), 2-amino-6-methylpyridine (4.3 g, 40.0 mmol), and hot water (50 °C, 22.5 mL) were slowly added to above mixture. The reaction solution was refluxed for 4 h at 135 °C and cooled to room temperature. 40percent water solution of NaOH was used to mediate pH to 7 and chloroform was used to extract the product. The organic phase was concentrated in vacuum to give the crude product and the final product was obtained by column chromatography (200-300 mesh, 3/1 ethyl acetate/petroleum ether) (3.0 g, 25.9percent yield). Characterization of 2-methyl-1,8-naphthyridine: HRMS (EI) m/z: calcd for C9H9N2 [M+H]+, 145.0766; found, 145.0768. 1H NMR (400 MHz; CDCl3; TMS) 9.08 (d, 1H), 8.13-8.16 (m, 1H), 8.08 (d, 1H), 7.43-7.45 (m, 1H), 7.28 (d, H), 2.82 (s, 3H). 13C NMR: deltaC (100 MHz, CDCl3): 163.1, 160.0, 153.3, 136.9, 136.7, 123.0, 121.4, 120.8, 25.7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With polyphosphoric acid; at 110.0℃; for 5.0h; | [02991 A mixture of 2-amino-6-picoline (324 mg, 3.0 rnrnol) and ethyl chloroacetate (594 rng, 3.60 mmol) in polyphosphoric acid (10 mL) was heated at 110 C for 5 hrs. After cooling to room temperature, the mixture was quenched with water (50 mL). The pH value was adjusted to 6-7 with aqueous K2C03. Then the new mixture was extracted with EA (50 mL x3).the organic layers were washed with brine (50 mL), dried over Na2SO4 and filtered. The filtrate was evaporated in vacuum to give 2-chloromethyl-6-methyl-pyrido[1,2-ajpyrimidin- 4-one (360 rng, yield: 58%) as yellow solid. [03001 ?H NMR (400 MHz, DMSO-d6): cS 7.68 (dd, J- 4.0, 1.2 Hz, 1H), 7.40 (d, J= 7.6 Hz, IH), 6.93 (d, J 6.8 Hz, 1H), 6.36 (s, 1H), 4.58 (s, 21-1), 2.93 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ferrous(II) sulfate heptahydrate; sulfuric acid; boric acid; sodium 3-nitrobenzenesulfonate; In water; at 50 - 135℃;Cooling with ice; Reflux; | Ice bath under conditions of 250 mLOf the three bottles by adding concentrated H2SO441 g (22 mL),Stir by addingSodium nitrobenzene sulfonate17.5 g (78 mmol),Boric acid2.4 g (39 mmol),FeSO4 · 7H2O 1.4 g (5 mmol)Glycerol 12.5 mL,2-amino-6-methylpyridine (4.3 g, 40 mmol)Mixed evenly after adding 22.5mL 50 warm water,in135 ° CUnder reflux2-3h,After cooling; with 50percent NaOH solution transferred to alkaline, filter,The aqueous solution was extracted three times with chloroform and the organic layer was dried over anhydrous MgSO4,The solvent was removed by rotary distillation to give the crude product which was recrystallized from cyclohexane to give 2-methylnaphthyridine,Ie probe reagent;The concentrated sulfuric acid concentration is 95-98percent; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a thermometer,Reflux condenser,Constant pressure dropping funnel and a mechanical stirrer 500mL four-necked flask,250 mL (3 mol) of 36percent hydrochloric acid was added,54 g (0.5 mol) of 2-amino-6-methylpyridine,12.7 g (0.05 mol) of iodine,30 g (0.5 mol) acetic acid.Turn on stirring and heatingMaintain the reaction bottle temperature 95-100 ,96.3 g (0.55 mol) of acrolein was evenly added dropwise over 3 hours,After the reaction was continued dropping 5h.Cooled to room temperature, carefully neutralized with 40percent aqueous sodium hydroxide to pH = 8,The aqueous phase was extracted with ethyl acetate and concentrated under reduced pressure to remove the solvent. The residue was distilled under reduced pressure to give 2-methyl-1,8-naphthyridine as a white crystal. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With NCS; | Example 172 Synthesis of 5-chloro-6-methylpyridin-2-amine. To a solution of 6-methylpyridin-2-amine (1.08 g, 1 mmol) in DMF (10 mL) was added NCS (1.34 g, 1 mmol), then the mixture was stirred at RT for 12 h. The mixture was treated with ice H2O and extracted with EtOAc (100 mL). The organic layer was washed with brine, dried over Na2SO4, concentrated to give the crude product which was purified with silica gel chromatography (PE/EA=2:1) to give 5-chloro-6-methylpyridin-2-amine as a yellow solid (750 mg, yield: 53%). ESI-MS [M+H]+: 142.9. |
Tags: 1824-81-3 synthesis path| 1824-81-3 SDS| 1824-81-3 COA| 1824-81-3 purity| 1824-81-3 application| 1824-81-3 NMR| 1824-81-3 COA| 1824-81-3 structure
Precautionary Statements-General | |
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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 |
Sorry,this product has been discontinued.
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