Structure of 37482-64-7
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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. : | 37482-64-7 |
Formula : | C7H9ClN2O |
M.W : | 172.61 |
SMILES Code : | CCOC1=CC(C)=NC(Cl)=N1 |
MDL No. : | MFCD00234338 |
InChI Key : | VEGXTHMAVSWQTH-UHFFFAOYSA-N |
Pubchem ID : | 15288671 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.43 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 43.31 |
TPSA ? Topological Polar Surface Area: Calculated from |
35.01 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.57 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.24 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.84 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.02 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.25 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.98 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.59 |
Solubility | 0.441 mg/ml ; 0.00255 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.61 |
Solubility | 0.423 mg/ml ; 0.00245 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.18 |
Solubility | 0.113 mg/ml ; 0.000655 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 |
-5.76 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) |
2.03 |
* 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 |
---|---|---|
In tetrahydrofuran; | EXAMPLE 10 4-Ethoxy-2-(1-imidazolyl)-6-methylpyrimidine In anhydrous tetrahydrofuran, 173 mg of <strong>[37482-64-7]2-chloro-4-ethoxy-6-methylpyrimidine</strong> was substituted with 68 mg of imidazole. The reaction mixture was treated according to the procedure of Example 5 to yield 103 mg of 4-ethoxy-2-(1-imidazolyl)-6-methylpyrimidine, recrystallized from a mixture of n-hexane and ethyl acetate, having a melting point of 115.5-116 C. NMR(CDCl3)delta: 1.13(3H,t,J=8 Hz), 2.44(3H,s), 4.50(2H,q,J=8 Hz), 6.43(1H,s), 7.20(1H,s), 7.90(1H,s), 8.63(1H,s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With NH-pyrazole; In tetrahydrofuran; | EXAMPLE 11 4-Ethoxy-6-methyl-2-(1-pyrazolyl)pyrimidine In anhydrous tetrahydrofuran, 173 mg of <strong>[37482-64-7]2-chloro-4-ethoxy-6-methylpyrimidine</strong> was substituted with 68 mg of pyrazole. The reaction mixture was treated according to the procedure of Example 5 to yield 110 mg of 4-ethoxy-6-methyl-2-(1-pyrazolyl)pyrimidine, an oily compound. NMR(CDCl3)delta: 1.40(3H,t,J=7 Hz), 2.40(3H,s), 4.50(2H,q,J=7 Hz), 6.4-6.6(2H,m), b 7.81(1H,bs), 8.28(1H,d,J=3 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With copper(l) iodide; 3,4,7,8-Tetramethyl-o-phenanthrolin; caesium carbonate; In N,N-dimethyl-formamide; at 50.0℃; for 3.0h;Inert atmosphere; | To a round bottom flask containing 600 mg (3.48 mmol) of <strong>[37482-64-7]2-chloro-4-ethoxy-6-methylpyrimidine</strong>, 489 mg (5.22 mmol) of azetidine hydrochloride, 131 mg (0.69 mmol) of CuI, 164 mg (0.69 mmol) of 3,4,7,8-tetramethyl-1,10-phenanthroline and 2.83 g (8.70 mmol) of Cs2CO3 was added 15 mL of dry, degassed DMF. The reaction mixture was stirred at 50 C for 3 h. The cooled reaction mixture was filtered through Celite and the Celite pad was washed with portions of CH2Cl2. The combined organic phase was washed with water and then with brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by flash chromatography on a silica gel column (15 * 3 cm). Elution with 19:1 hexane/EtOAc followed by 9:1 hexane/EtOAc afforded 18 as a colorless solid: yield 565 mg (84%); mp 42-43 C; silica gel TLC Rf 0.29 (3:2 hexane/EtOAc); 1H NMR (CDCl3) delta 1.24 (t, 3H, J = 7.2 Hz), 2.16 (s, 3H), 2.20 (quint, 2H, J = 7.6 Hz), 4.01 (t, 4H, J = 7.6 Hz), 4.20 (q, 2H, J = 7.2 Hz) and 5.73 (s, 1H); 13C NMR (CDCl3) delta 14.4, 16.1, 23.9, 49.9, 61.2, 95.0, 163.0, 167.7 and 170.1; mass spectrum (APCI), m/z 194.1289 (M+H)+ (C10H16N3O requires m/z 194.1293). |
84% | With copper(l) iodide; 3,4,7,8-Tetramethyl-o-phenanthrolin; caesium carbonate; In N,N-dimethyl-formamide; at 50.0℃; for 3.0h; | To a round bottom flask containing 600 mg (3.48 mmol) of 39, 489 mg (5.22 mmol) of azetidine hydrochloride, 131 mg (0.69 mmol) of Cul, 164 mg (0.69 mmol) of 3,4,7,8-tetramethyl- 1,10-phenanthroline and 2.83 g (8.70 mmol) of Cs2CO3 was added 15 mL of dry degassed DMF. The reaction mixture was stirred at 50 C for 3 h. The mixture was allowed to cool to room temperature and then filtered through Celite and the Celite pad was washed with CH2C12. The combined organic phase was washed with water and then with brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by flash chromatography on a silica gel column (15 x 3 cm). Elution with 19:1 hexane-EtOAc followed by 9:1 hexane-EtOAc afforded 40 as a colorless solid:yield 565 mg (84%); mp 42-43 C; silica gel TLC Rf 0.29 (3:2 hexane-EtOAc); ?H NMR (CDC13, 400 MHz) 8 1.24 (t, 3H,J 7.2 Hz), 2.16 (s, 3H), 2.20 (quint, 2H,J 7.6 Hz), 4.01 (t, 4H,J 7.6 Hz), 4.20 (q, 2H,J= 7.2 Hz) and 5.73 (s, 1H); ?3C NMR (CDC13, 100 MHz) 6 14.4, 16.1,23.9,49.9,61.2, 95.0, 163.0, 167.7 and 170.1; mass spectrum (APCI), rn/z 194.1289 (M+H) (C,0H,6N30 requires 194.1293). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With caesium carbonate; for 48.0h;Reflux; | Cs2CO3 (6.6 g, 20.2 mmol) and 46 mL of EtOH were added to 2,4-dichloro-6-)pyrimidine (3.0 g, 18.4mmol), and the mixture was stirred for 48 hours under reflux. After filtering solids, the filtrate was purified by columnchromatography to obtain the title compound (1.88 g, 59 %).1H-NMR (CDCl3) delta 6.47 (1H, s), 4.41 (2H, q), 2.42 (3H, s), 1.39 (3H, t) |
51% | With sodium hydride; In tetrahydrofuran; mineral oil; at 20.0℃; for 5.0h;Inert atmosphere; | To a stirred solution containing 2.01 g (12.3 mmol) of 2,4-dichloro-6-methylpyrimidine in 40 mL of anhydrous THF was added 927 mg (38.6 mmol) of NaH (60% suspension in oil) and 392 muL (12.9 mmol) of EtOH. The reaction mixture was stirred at room temperature for 5 h and then poured slowly into 200 mL of water. The crude reaction mixture was extracted with two 300-mL portions of EtOAc. The combined organic phase was washed with brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (15 * 6 cm). Elution with 19:1 hexane/EtOAc afforded 2-chloro-4-ethoxy-6-methylpyrimidine as a colorless solid: yield 2.16 g (51%); mp 37-38 C; silica gel TLC Rf 0.41 (4:1 hexane/EtOAc); 1H NMR (CDCl3) delta 1.38 (t, 3H, J = 7.2 Hz), 2.42 (s, 3H), 4.42 (d, 2H, J = 7.2 Hz) and 6.46 (s, 1H); 13C NMR (CDCl3) delta 14.4, 23.8, 63.5, 105.7, 159.8, 169.8 and 170.9; mass spectrum (APCI), m/z 173.0477 (M+H)+ (C7H10N2OCl requires m/z 173.0482). |
51% | With sodium hydride; In tetrahydrofuran; mineral oil; at 20.0℃; for 5.0h; | To a stirred solution containing 2.01 g (12.3 mmol) of 2,4-dichloro-6-methylpyrimidine in 40 mL of anhydrous THF was added 927 mg (38.6 mmol) of NaH (60% suspension in oil) and 392 jiL (12.9 mmol) of EtOH. The reaction mixture was stirred for 5 h at room temperature and then slowly poured into 200 mL of water. The crude was extracted with two 300-mL portions of EtOAc. The combined organic phase was washed with brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (15 x 6 cm). Elution with 19:1 hexane-EtOAc afforded 39 as a colorless solid: yield 2.16 g (51%); mp 37-38 C; silica gel TLC Rf 0.41 (4:1 hexane-EtOAc); ?H NMR (CDC13, 400 MHz) 1.38 (t, 3H, J= 7.2 Hz), 2.42 (s, 3H), 4.42 (d, 2H, J= 7.2 Hz) and 6.46 (s, 1H); ?3C NMR (CDCI3, 100 MHz) 14.4, 23.8,63.5, 105.7, 159.8, 169.8 and 170.9; mass spectrum (APCI), m/z 173.0477 (M+H) (C7H10N2OC1 requires 173.0482). |
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