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Chemical Structure| 37482-64-7

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Product Details of [ 37482-64-7 ]

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

Safety of [ 37482-64-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 37482-64-7 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

35.01 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

2.57
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.24
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.84
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.02
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.98

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.59
Solubility 0.441 mg/ml ; 0.00255 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.61
Solubility 0.423 mg/ml ; 0.00245 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-3.18
Solubility 0.113 mg/ml ; 0.000655 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.76 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.03

Application In Synthesis of [ 37482-64-7 ]

* 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.

  • Downstream synthetic route of [ 37482-64-7 ]

[ 37482-64-7 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 5424-21-5 ]
  • [ 141-52-6 ]
  • [ 37482-64-7 ]
  • 2
  • [ 288-13-1 ]
  • [ 37482-64-7 ]
  • 4-ethoxy-6-methyl-2-(1-pyrazolyl)pyrimidine [ No CAS ]
  • 3
  • [ 288-32-4 ]
  • [ 37482-64-7 ]
  • 4-ethoxy-2-(1-imidazolyl)-6-methylpyrimidine [ No CAS ]
YieldReaction ConditionsOperation 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).
  • 5
  • [ 37482-64-7 ]
  • 4-ethoxy-6-methyl-2-(1-pyrazolyl)pyrimidine [ No CAS ]
YieldReaction ConditionsOperation 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).
  • 6
  • [ 37482-64-7 ]
  • 2-(azetidin-1-yl)-4-ethoxy-6-hexadecylpyrimidine [ No CAS ]
  • 7
  • [ 37482-64-7 ]
  • 2-(azetidin-1-yl)-5-bromo-4-ethoxy-6-hexadecylpyrimidine [ No CAS ]
  • 8
  • [ 37482-64-7 ]
  • 2-(Azetidin-1-yl)-4-ethoxy-6-hexadecylpyrimidin-5-ol [ No CAS ]
  • 9
  • [ 37482-64-7 ]
  • [ 78797-58-7 ]
  • 2-(azetidin-1-yl)-4-ethoxy-6-methylpyrimidine [ No CAS ]
YieldReaction ConditionsOperation 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).
  • 10
  • [ 5424-21-5 ]
  • [ 64-17-5 ]
  • [ 37482-64-7 ]
YieldReaction ConditionsOperation 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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