Structure of 89026-78-8
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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. : | 89026-78-8 |
Formula : | C6H7ClN2 |
M.W : | 142.59 |
SMILES Code : | CNC1=NC(Cl)=CC=C1 |
MDL No. : | MFCD00234196 |
InChI Key : | VPGPNOQDNGMIKA-UHFFFAOYSA-N |
Pubchem ID : | 10290849 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319-H335 |
Precautionary Statements: | P261-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 | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 38.55 |
TPSA ? Topological Polar Surface Area: Calculated from |
24.92 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.71 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.13 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.59 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.16 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.68 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.65 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.49 |
Solubility | 0.458 mg/ml ; 0.00321 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.28 |
Solubility | 0.74 mg/ml ; 0.00519 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.06 |
Solubility | 0.126 mg/ml ; 0.000881 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 |
-5.66 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 |
1.0 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) |
1.75 |
* 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 |
---|---|---|
94% | With copper(l) iodide; In water; at 180.0℃; for 2.0h;Sealed tube; Microwave irradiation; | General procedure: Compounds I-VII (4.22 mmol), catalytic amounts of CuI (10 mg, 0.052 mmol) and water (100 muL) were treated with 6equiv of the respective amine and sealed in a 5 mL microwave vial. Pd(PPh3)4 (10 mg, 0.008 mmol) was added in the case of anilines. After the reaction was completed (see Table 1), 2 equiv of solid K2CO3 were added. The resulting product was obtained after filtration and washing with water as an analytically pure crystalline solid. Otherwise all volatiles were then evaporated and purified by flash column chromatography (A) or bulb-to-bulb distillation (B). In the case of methylamine and ethylamine the corresponding aqueous solution was used without extra water addition. |
With sodium hydroxide; In water; at 120.0℃; for 16.0h; | To a stirring solution of 2,6-dichloro-pyridine (15 g, 0.10 mol) and methylamine (40 wt %, H2O, 20 mL) in a sealed tube, NaOH (8 g, 0.20 mol) was added, the heterogeneous solution was heated at 120 C. for 16 h, the mixture was cooled down to RT before poured into 200 mL ice-H2O. After filtration, the title productproduct was collected as an off-white solid. MS m/z 143 (MH)+. | |
With sodium hydroxide; In water; at 80.0℃; for 16.0h; | To a stirred solution of 2,6-dichloropyridine (1.0 g, 6.76 mmol) in methylamine (40% in water) (1.3 ml) was added NaOH (0.54 g, 13.5 mmol) at rt. The reaction mixture was heated at 80C for 16 h. The reaction mixture was cooled to rt, poured into cold water (20 ml). The obtained precipitates were collected by filtration, washed with water (15 ml) and dried under vacuum yielding 6-chloro-N- methylpyridin-2-amine (0.399 g, 2.80 mmol). This material was used for the next step without furtherpurification. LCMS: Method C, 1.82 mm, MS: ES+ 143.03; ?H NMR (400 MHz, DMSO-d6) (5ppm 7.38(dd, J=7.6 Hz, 8.0 Hz, 1 H), 6.90 (d, J4.0 Hz, 1 H), 6.48 (d, J=7.6 Hz, 1 H), 6.37 (d, J=8.4 Hz, 1 H), 2.73(d, J=4.8 Hz, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; for 3.0h;Heating / reflux; | 6-Chloro-N-methylpyridin-2-mine (11.5 g, 0.081 mol) and phenylboronic acid (16 g, 0.131 mol) were mixed in 160 mL DME, after degassed by N2 for 10 min, 1,1-bis(diphenylphosphino)ferrocenedichloropalladium(II) (5 g, 6.12 mmol) was mixed, the heterogeneous solution was heated to reflux for 3 h. The mixture was concentrated under vacuum and the resulting oil was poured into saturated ammonium chloride and extracted (EtOAc, 2*). The combined organic layers were washed with saturated sodium bicarbonate, followed by brine. The resulting organic layers collected, dried over Na2SO4 and concentrated in vacuum. The crude product was purified with flash column chromatography (4:1 hexane/EtOAc) to give the title compound as an off-white solid. MS m/z 185 (MH)+. | |
0.308 g | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In ethanol; water; toluene; at 120.0℃; for 16.0h;Inert atmosphere; | To a stirred solution of <strong>[89026-78-8]6-chloro-N-methylpyridin-2-amine</strong> (0.3 g, 2.10 mmol) in toluene:EtOH:water (1:1:1; 3 ml) was added Cs2CO3 (1.37 g, 4.21 mmol) and phenylboronic acid (0.385 g, 3.16 mmol) at rt. The reaction mixture was degassed for 30 mm before adding Pd(PPh3)4 (0.121 g, 0.105 mmol) at a The reaction mixture was heated at 120C for 16 h. The resulting mixture was cooled to rt, diluted with water (20 ml) and extracted with EtOAc (3 x 25 ml). The combined organic phase was washed with water (20 ml). The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting crude material was purified by flash chromatography (3-7% EtOAc in hexane) yielding N-methyl-6-phenylpyridin-2-amine (0.308 g, 1.67 mmol). LCMS:Method C, 1.48 mi MS: ES+ 185.14; ?H NMR (400 MHz, CDC13) (5ppm 7.97 - 8.02 (m, 2 H), 7.55 (t, J=8.0 Hz, 1 H), 7.44 - 7.52 (m, 2 H), 7.37 - 7.41 (m, 1 H), 7.06 (d, J=7.6 Hz, 1 H), 6.39 (d, J8.4 Hz, 1 H), 3.00 (s, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 3 In the same reaction apparatus as in Example 1, 25 g of 2,6-dichloropyridine and 60 ml of 40% conc. methylamine aqueous solution were charged and were subjected to reacting each other at 120 C. for 5 hours. After completion of the reaction, the autoclave was cooled and the contents thereof was taken out, and then solid was collected through filtration. Then, this solid was recrystallized from n-hexane to give 22.7 g of 2-chloro-6-methylaminopyridine of m.p. 63.5-64.5 C. Then, in the same reaction apparatus as in Example 1, 20 g of 2-chloro-6-methylaminopyridine, 11.5 g of sodium hydroxide and 80 ml of methanol were charged, and they were subjected to reacting each other at 170 C. for 5 hours. After completion of the reaction, the autoclave was cooled and the contents thereof were taken out, and solid was removed by filtration. Then, methanol was distilled out of the filtrate and, after adding water to the residue, it was subjected to extraction with ether. The ether solution of the extract was dried over anhydrous magnesium sulfate and, after distilling out ether, the residue was subjected to vacuum distillation to give 15.6 g of 2-methoxy-6-methylaminopyridine of b.p. 88-92 C./5 mmHg. Yield of 2-methoxy-6-methylaminopyridine was 80.5%, calculated from the base of 2-chloro-6-methylaminopyridine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With sodium hexamethyldisilazane; In tetrahydrofuran; at -20.0℃; for 2.0h; | 2-Chloro-N-(6-chloropyridin-2-yl)-N-methyl-pyrimidin-4-amine used as starting material was made as follows: NaHMDS (1.5 ml, 1.5 mmol, IN in THF) was added dropwise to a mixture of 2-chloro-6- methylaminopyridine (142 mg, 1 mmol, German Patent, DE3318560, p 9) and 2,4- dichloropyrimidine (222 mg, 1.5 mmol) in THF (20 ml) cooled at -200C. The mixture was stirred at -200C for 2 hours. Acetic acid (a few drops) were added and the mixture was concentrated. The mixture was taken in DCM, filtered and concentrated. The residue was purified by chromatography on silica gel (eluant: 40% to 50% ethyl acetate in petroleum ether) to give 2-chloro-N-(6-chloropyridin-2-yl)-N-methyl-pyrimidin-4-amine (86 mg, 34%). NMR Spectrum: (CDCl3) 3.61 (s, 3H), 6.93 (d, IH), 7.18 (d, IH), 7.28 (m, IH), 7.72 (t, IH), 8.17 (d, IH); Mass spectrum: MH+ 255. |
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