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CAS No. : | 152398-05-5 |
Formula : | C6H8N2O |
M.W : | 124.14 |
SMILES Code : | OCC1=C(N)C=NC=C1 |
MDL No. : | MFCD06658330 |
InChI Key : | VXHFPFMVXWCZLH-UHFFFAOYSA-N |
Pubchem ID : | 14950620 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 34.77 |
TPSA ? Topological Polar Surface Area: Calculated from | 59.14 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 0.95 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | -0.16 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 0.01 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | -0.75 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 0.49 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 0.11 |
Log S (ESOL):? ESOL: Topological method implemented from | -0.94 |
Solubility | 14.4 mg/ml ; 0.116 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (Ali)? Ali: Topological method implemented from | -0.63 |
Solubility | 29.3 mg/ml ; 0.236 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -1.45 |
Solubility | 4.39 mg/ml ; 0.0354 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 | No |
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 | -7.17 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) | 1.06 |
* 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 |
---|---|---|
85% | With manganese(IV) oxide; In chloroform; at 20℃; for 48h; | Step 3: [MN02] (29 g, 334 [MMOL)] was added, in one portion, at RT, to a suspension of <strong>[152398-05-5]3-amino-4-hydroxymethyl pyridine</strong> (5.0 g, 40.3 [MMOL)] in [CHC13] (500 ml) with good stirring. After 2 days, the solid was filtered through a pad of Celite and washed with [CHC13.] Removal of the solvent using reduced pressure yielded 4.2 g (85%) of a yellow solid. |
85% | With manganese(IV) oxide; In chloroform; at 20℃; for 48h; | Manganese dioxide (29 gr.; 334 mmoles) was added, in one portion, at room temperature, to a suspension of <strong>[152398-05-5]3-amino-4-hydroxymethyl pyridine</strong> 290 (5.0 gr.; 40.3 mmoles) in 500 ml of chloroform with good stirring. After two days, the solid is filtered through a pad of Celite and washed with chloroform. Removal of the solvent using reduced pressure yielded 4.2 grams (85%) of Compound 291 as a yellow solid. |
10.1 g | With manganese(IV) oxide; In chloroform; at 20℃; for 18h; | Reference Example 39-1 3-Aminopyridine-4-carboaldehyde A solution of (3-aminopyridin-4-yl)-methanol (10.4 g) and manganese dioxide (50.3 g) in chloroform (100 mL) was stirred at room temperature for 18 hours. The reaction solution was filtered through Celite and concentrated to give the title compound (10.1 g). LC-MS ([M+H]+/Rt (min)): 123.0/0.218 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 20℃; for 48h; | Step 2: Solid compound 61 (9.5 g, 69 [MMOL)] was carefully added in 3 aliquots to a slurry of LiAIH4 (9.5 g, 250 [MMOL)] in dry THF (200 [ML).] The resulting hot mixture was stirred at RT for 2 days. After cooling in an ice bath, the reaction was quenched with careful sequential dropwise addition of water (10 [ML),] followed by 15percent aqueous [NAOH] (10 [ML),] then by water (30 [ML).] The resulting solid was filtered through a pad of Celite and washed several times with THF. The oil obtained after evaporation of the solvent solidified on standing. The reaction mixture was purified by flash chromatography on silica gel using 5percent CH30H (NH3) /EtOAc as eluent, yielding 6.21 g (72percent) of 62. LC-MS: m/z = 125 (M+1). |
72% | Solid Compound 289 (9.5 gr.; 69 mmoles) was carefully added in three aliquots to a slurry of lithium aluminum hydride (9.5 gr.; 250 mmoles) in 200 ml of dry tetrahydrofuran. The resulting hot mixture was stirred at room temperature for two days. After cooling in an ice bath, the reaction was quenched with very careful sequential dropwise addition of 10 ml of water, followed by 10 ml of 15percent aqueous NaOH, then by 30 ml of water. The resulting solid was filtered through a pad of Celite and washed several times with THF. The oil obtained after evaporation of the solvent, solidified on standing. The reaction mixture was purified by flash chromatography on silica gel using 5percentMeOH(NH3)/EtOAc as eluent yielding 6.21 (72percent) of Compound 290 . LC-MS: m/z = 125 (M+l). | |
3- Aminoisonicotinic acid (1 g, 7.24 mmol) was carefully added in 3 aliquots to a slurry of UAIH4 (0.99 g, 26.1 mmol) in dry tetrahydrofuran (40 ml). The resulting mixture was stirred at 15°C overnight. After cooling in an ice bath, the reaction mixture was quenched with careful addition of water (1 ml) dropwise, followed by 15percent aqueous NaOH (1 ml), and then water (3 ml). The resulting solid was filtered, and washed several times with tetrahydrofuran. The filtrate was concentrated to give oil, which was purified by flash chromatography on silica gel using 5percent CH3OH <NH3) /ethyl acetate as eluent to yield the title compound as a yellow oil. 610 mg.MS (electrospray): m/z [M+H]+ = 125 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bromine; In tetrahydrofuran; methanol; sodium hydroxide; water; acetic acid; | EXAMPLE 29 3,4 Pyridine-dicarboximide 288 (10.0 g; 67.5 mmoles) was dissolved in 162 g. of 10% aqueous NaOH and the solution was cooled to an internal temperature of 7 C. in an ice-salt bath. Bromine (3.6 ml; 70 mmoles) was added dropwise. After the addition, the solution was heated for 45 minutes at a bath temperature of 80-85 C. The yellow solution was then cooled to an internal temperature of 37 C., then 17 ml of glacial acetic acid were added dropwise to a pH of 5.5. The resulting mixture was saved overnight in a refrigerator. The solid formed was filtered and washed with 5 ml of water and 5 ml of methanol. The reaction yielded 6.35 g. of product 289 melting at 280-285 C. (decomp.). Solid Compound 289 (9.5 gr.; 69 mmoles) was carefully added in three aliquots to a slurry of lithium aluminum hydride (9.5 gr.; 250 mmoles) in 200 ml of dry tetrahydrofuran. The resulting hot mixture was stirred at room temperature for two days. After cooling in an ice bath, the reaction was quenched with very careful sequential dropwise addition of 10 ml of water, followed by 10 ml of 15% aqueous NaOH, then by 30 ml of water. The resulting solid was filtered through a pad of Celite and washed several times with THF. The oil obtained after evaporation of the solvent, solidified on standing. The reaction mixture was purified by flash chromatography on silica gel using 5%MeOH(NH3)/EtOAc as eluent yielding 6.21 (72%) of Compound 290. LC-MS: m/z=125 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 15℃; | Neat <strong>[152398-05-5](3-aminopyridin-4-yl)methanol</strong> (may be prepared as described in Description 81 ; 103 mg, 0.83 mmol) was added in one charge to a stirred suspension of 2- [(phenylmethyl)oxy]-5-(4-pyridiny.)benzoic acid (may be prepared as described in Description 79; 180 mg, 0.59 mmol), EDC (226 mg, 1.18 mmol), HOBT (181 mg, 1.179 mmol) and triethylamine (0.16 ml, 1 .18 mmol) in N,N-dimethylformamide (1.5 ml) in air at 15 C. The reaction mixture was stirred at 15 C overnight. 100 ml of water was added. The solid was filtered, and then purified by prep-HPLC (instrument: Giison-281 .Column: Shimadzu 5um: 250*20mm*2, Mobile Phase : A: 10mMol/LNH4HCO3, B: CH3CN, Flow rate: 30.0ml/L, Gradient: B: 43-55% in 0-7.2 RT= 7.5min, 0.5) to yield the title compound as a white solid. 57 mg.1H NMR (400MHz, DMSO-cf6): 10.29 (s, 1 H), 8.90-8.92 (m, 2H), 8.62-8.63 (m, 2H), 8.39-8.40 (m, 1 H), 8.24-8.25 (m, 1 H), 7.96-7.99 (m, 1 H), 7.73-7.75 (m, 2H), 7.53-7.55 (m, 2H), 7.47-7.48 (m, 1 H), 7.33-7.42 (m, 4H), 5.56 (t, 1 H, J=5.2), 5,46 (s, 2H), 4.53 (d, 2H, J=5.2).MS (electrospray): m/z [M+H]+ = 412.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride; In tetrahydrofuran; | Intermediate C: 1-(4-((3-Aminopyridin-4-yl)methoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea To a solution of <strong>[152398-05-5](3-amino-pyridin-4-yl)-methanol</strong> (13) (4.00 g, 32.2 mmol) in anhydrous THF (160 mL) at 0 C. was added sodium hydride (1.55 g, 38.7 mmol, 60 wt %). After stirring for 20 min, 1-fluoro-4-nitronaphthalene (14) (6.16 g, 32.2 mmol) was added, the ice bath was removed and the reaction mixture left to warm to RT and stirred for 12 hr. The reaction mixture was partitioned between EtOAc (200 mL) and saturated aq NaHCO3 solution (150 mL). The remaining yellow solid was collected by filtration and washed sequentially with water (50 mL), MeOH (50 mL) and diethyl ether (100 mL) and was identified as the desired product by LC-MS and 1H NMR. The filtrate was returned to a separating funnel; the organic phase was collected and washed with brine (100 mL), dried and concentrated in vacuo to afford an orange residue. Trituration of the orange residue with MeOH (200 mL) afforded an orange solid which was washed with diethyl ether (200 mL). LC-MS and 1H NMR analysis of the orange solid was identical to that observed for the insoluble solid obtained earlier. The two products were combined to afford 4-((4-nitronaphthalen-1-yloxy)methyl)pyridin-3-amine (15) (7.80 g, 77%): m/z 296 (M+H)+ (ES+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | To a solution of <strong>[152398-05-5](3-amino-pyridin-4-yl)-methanol</strong> (13) (4.00 g, 32.2 mmol) in anhydrous THF (160 mL) at 0 C. was added sodium hydride (1.55 g, 38.7 mmol, 60 wt %). After stirring for 20 min, 1-fluoro-4-nitronaphthalene (14) (6.16 g, 32.2 mmol) was added, the ice bath was removed and the reaction mixture left to warm to RT and stirred for 12 hr. The reaction mixture was partitioned between EtOAc (200 mL) and saturated aq NaHCO3 solution (150 mL). The remaining yellow solid was collected by filtration and washed sequentially with water (50 mL), MeOH (50 mL) and diethyl ether (100 mL) and was identified as the desired product by LC-MS and 1H NMR. The filtrate was returned to a separating funnel; the organic phase was collected and washed with brine (100 mL), dried and concentrated in vacuo to afford an orange residue Trituration of the orange residue with MeOH (200 mL) afforded an orange solid which was washed with diethyl ether (200 mL). LC-MS and 1H NMR analysis of the orange solid was identical to that observed for the insoluble solid obtained earlier. The two products were combined to afford 4-((4-nitronaphthalen-1-yloxy)methyl)pyridin-3-amine (15) (7.80 g, 77%): m/z 296 (M+H)+ (ES+). |
Tags: 152398-05-5 synthesis path| 152398-05-5 SDS| 152398-05-5 COA| 152398-05-5 purity| 152398-05-5 application| 152398-05-5 NMR| 152398-05-5 COA| 152398-05-5 structure
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