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Structure of 5270-94-0

Chemical Structure| 5270-94-0

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Product Details of [ 5270-94-0 ]

CAS No. :5270-94-0
Formula : C6H8N2O2
M.W : 140.14
SMILES Code : COC1=CC(OC)=NC=N1
MDL No. :MFCD00955844
InChI Key :FPSPPRZKBUVEJQ-UHFFFAOYSA-N
Pubchem ID :259821

Safety of [ 5270-94-0 ]

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

Computational Chemistry of [ 5270-94-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 35.02
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

44.24 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.57
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

0.96
Log Po/w (WLOGP)?

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

0.49
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.

-0.11
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

0.85
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.75

Water Solubility

Log S (ESOL):?

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

-1.63
Solubility 3.32 mg/ml ; 0.0237 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.48
Solubility 4.68 mg/ml ; 0.0334 mol/l
Class?

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

Very 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

-1.88
Solubility 1.84 mg/ml ; 0.0132 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

No
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.

-6.47 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)

1.72

Application In Synthesis of [ 5270-94-0 ]

* 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 [ 5270-94-0 ]

[ 5270-94-0 ] Synthesis Path-Downstream   1~25

  • 1
  • [ 100-52-7 ]
  • [ 5270-94-0 ]
  • [ 126327-70-6 ]
  • 2
  • [ 98-88-4 ]
  • [ 5270-94-0 ]
  • [ 126327-71-7 ]
  • 3
  • [ 75-77-4 ]
  • [ 5270-94-0 ]
  • [ 126327-69-3 ]
  • 4
  • [ 5270-94-0 ]
  • [ 74-88-4 ]
  • [ 13566-63-7 ]
  • 6
  • [ 13223-25-1 ]
  • [ 128276-49-3 ]
  • [ 5270-94-0 ]
  • 9
  • diimidate [ No CAS ]
  • ethereal ammonia [ No CAS ]
  • aqueous K2 CO3 [ No CAS ]
  • acetyl choloride [ No CAS ]
  • dimethyl-1,3-propanediimidate dihydrochloride [ No CAS ]
  • [ 75-09-2 ]
  • [ 584-08-7 ]
  • [ 2258-42-6 ]
  • [ 5270-94-0 ]
YieldReaction ConditionsOperation in experiment
With ammonia; sodium formate; In diethyl ether; water; EXAMPLE 1 4,6-Dimethoxypyrimidine 5.0 g of dimethyl-1,3-propanediimidate dihydrochloride was added by vigorous stirring to a mixture of 25 ml of CH2 Cl2 and 25 ml of aqueous K2 CO3 solution (300 g of K2 CO3 /1 solution). After 5 minutes the organic phase was separated and the aqueous phase was extracted with 10 ml of Ch2 Cl2. The combined organic phases were dried on Na2 SO4 and filtered. A freshly prepared mixture of 2.5 g of formyl acetate [produced from acetyl choloride and sodium formate according to Muramatsu et al., Bull. Chem. Soc., Japan, 38, (1965), p. 244] in 2 ml of diethyl ether was added at 0 C. to the above solution of the diimidate and stirred for two hours at this temperature. A small amount of ammonia gas was introduced (or ethereal ammonia solution was added) so that the reaction mixture showed an approximately neutral reaction with moistened pH paper. After another hour of stirring at 0 C., 10 ml of water was added. The organic phase was separated, dried on Na2 SO4 and gently concentrated by evaporation. After distillation in a bulb tube furnace (product fraction: 110 C./16 mbar) the product was obtained as a colorless oil, which gradually solidified when allowed to stand. The yield of the product was: 2.4 g, which was 66.3 percent relative to the dihydrochloride used with a product content of 96 percent (GC).
  • 10
  • [ 5270-94-0 ]
  • [ 4319-77-1 ]
YieldReaction ConditionsOperation in experiment
With N-Bromosuccinimide; acetic anhydride; at 100℃; for 5.16h; B. Preparation of 5-bromo-<strong>[5270-94-0]4,6-dimethoxypyrimidine</strong> To the solution of <strong>[5270-94-0]4,6-dimethoxypyrimidine</strong> (5 g, 35.7 mmol) in HOAc (20 mL) at room temperature under argon was added Ac2O (4.6 g, 44.6 mmol). The resulting solution was heated at 100 C. for 10 min and then NBS (7.9 g, 44.6 mmol) was added. Heating was continued at 100 C. for 5 h. Analysis by HPLC/MS indicated that the reaction was complete. After the reaction mixture was cooled to room temperature, water (50 mL) was added. The resulting precipitate was collected by filtration and further washed with water (15 mL*3), then dried under vacuum. The title compound (7.5 g) was obtained as a white solid. 1H NMR (CDCl3): delta 4.05 (s, 6H), 8.32 (s, 1H). 13C NMR (CDCl3): delta 55.2, 89.0, 154.9, 166.8.
  • 11
  • [ 1193-21-1 ]
  • [ 124-41-4 ]
  • [ 5270-94-0 ]
YieldReaction ConditionsOperation in experiment
In methanol; at 20 - 65℃; for 24.08h; Preparation of Intermediate 4-chloro-6-(4-chlorophenyl)-5-(pyridin-4-yl)pyrimidine; A. Preparation of 4,6-dimethoxypyrimidine; To a suspension of 4,6-dichloropyrimidine (6.5 g, 43.9 mmol) in methanol (30 mL) at room temperature under argon was added NaOMe (7.1 g, 132 mmol) over 5 min. The resulting suspension was heated at 65 C. under argon for 24 h. Analysis by HPLC/MS indicated that the reaction was complete. Most of the solvent was removed under reduced pressure, then 1 M aqueous HCl (50 mL) and CH2Cl2 (50 mL) were added to the residue. The layers were separated and the organic phase was washed with saturated aqueous NaCl (30 mL), then dried (Na2SO4), filtered and evaporated. The crude product was purified by silica gel column chromatography eluted with ethyl acetate-hexanes to obtain the title compound (5.76 g) as a low melting solid. See also Synthesis 1998, page 36.
  • 12
  • [ 5270-94-0 ]
  • 5-iodo-4,6-dimethoxypyrimidine [ No CAS ]
  • 13
  • [ 1521-51-3 ]
  • [ 5270-94-0 ]
  • 2-(cyclohex-2-en-1-yl)-4,6-dimethoxypyrimidine [ No CAS ]
  • 14
  • [ 696-62-8 ]
  • [ 5270-94-0 ]
  • 4,6-dimethoxy-2-(4-methoxyphenyl)pyrimidine [ No CAS ]
  • 15
  • [ 1296137-49-9 ]
  • [ 5270-94-0 ]
  • 5-(trans-2-((tert-butyldimethylsilyl)oxy)cyclohexyl)-4,6-dimethoxypyrimidine [ No CAS ]
  • 16
  • TMG•CF3I [ No CAS ]
  • [ 5270-94-0 ]
  • 4,6-dimethoxy-5-(trifluoromethyl)pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With dipotassium peroxodisulfate; copper(II) acetate monohydrate; acetic acid; at 90℃; for 24h;Inert atmosphere; Sealed tube; [00238] <strong>[5270-94-0]4,6-Dimethoxypyrimidin</strong>e (35.0 mg, 0.250 mmol, 1.00 eq), K2S20g (270 mg, 1.00 mmol, 4.00 eq) and Cu(OAc)2 FontWeight="Bold" FontSize="10" H20 (100 mg, 0.500 mmol, 2.00 eq) were dissolved in glacial acetic acid (2.00 mL). TMG FontWeight="Bold" FontSize="10" CF3I (0.100 mL, 0.500 mmol, 2.00 eq) was added, the reaction vessel was sealed and heated at 90 C for 24 hours. The reaction mixture was diluted with saturated aqueous sodium carbonate (50 mL) and the resulting mixture extracted with ethyl acetate (3 x 25 mL). The combined ethyl acetate extracts were dried (MgS04) and concentrated in vacuo. The residue was purified by preparative TLC eluting with 10% EtOAc/hexanes to afford 26.0 mg (0.125 mmol, 50%) 14 as a white solid. [00239] R/= 0.55 (10% EtOAc/hexanes). NMR spectroscopy: 1H NMR (400 MHz, CDC13, 23 C) delta ppm 8.48 (s, 1H), 4.05 (s, 6H). 13C NMR (125 MHz, CDC13, 23 C) delta ppm 167.9, 158.8, 122.8 (q, JCF = 273 Hz), 95.5 (q, JCF = 35 Hz), 55.1. 19F NMR (376 MHz, CDC13, 23 C) delta ppm -56.9. Mass spectrometry: HRMS (APCI) (m/z): Calcd for [C7H7F3N202]+, [M+]: 208.0460. Found, 208.0466.
  • 17
  • TMG•CF3CF2I [ No CAS ]
  • [ 5270-94-0 ]
  • 4,6-dimethoxy-5-(pentafluoroethyl)pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% With dipotassium peroxodisulfate; copper(II) acetate monohydrate; acetic acid; at 90℃; for 24h;Inert atmosphere; Sealed tube; [00240] <strong>[5270-94-0]4,6-Dimethoxypyrimidin</strong>e (35.0 mg, 0.250 mmol, 1.00 eq), K2S208 (270 mg, 1.00 mmol, 4.00 eq) and Cu(OAc)2 FontWeight="Bold" FontSize="10" H20 (100 mg, 0.500 mmol, 2.00 eq) were dissolved in glacial acetic acid (2.00 mL). TMG FontWeight="Bold" FontSize="10" CF3CF2I (0.110 mL, 0.500 mmol, 2.00 eq) was added, the reaction vessel was sealed and heated at 90 C for 24 hours. The reaction mixture was diluted with saturated aqueous sodium carbonate (50 mL) and the resulting mixture extracted with ethyl acetate (3 x 25 mL). The combined ethyl acetate extracts were dried (MgS04) and concentrated in vacuo. The residue was purified by preparative TLC eluting with 10% EtOAc/hexanes to afford 33.1 mg (0.128 mmol, 51%) 15 as a white solid. [00241] R/= 0.58 (10% EtOAc/hexanes). NMR spectroscopy: 1H NMR (400 MHz, CDC13, 23 C) delta ppm 8.47 (s, 1H), 4.01 (s, 6H). 13C NMR (125 MHz, CDC13, 23 C) delta ppm 168.9, 159.2, 119.4 (qt, JCF = 288, 39 Hz), 112.7 (tq, JCF = 258, 41 Hz), 93.3 (t, JCF = 24 Hz), 55.0. 19F NMR (376 MHz, CDC13, 23 C) delta ppm -85.0 (s, 3F), -110.6 (s, 2F). Mass spectrometry: HRMS (APCI) (m/z): Calcd for [C8H7F5N202]+, [M+]: 258.0428. Found, 258.0434.
  • 18
  • [ 5270-94-0 ]
  • (3E,5E)-3,5-bis({4-[(4,6-dimethoxypyrimidin-2-yl)oxy]phenyl}methylidene)-1-methylpiperidin-4-one [ No CAS ]
  • 19
  • [ 5270-94-0 ]
  • (2E,5E)-2,5-bis({4-[(4,6-dimethoxypyrimidin-2-yl)oxy]phenyl}methylidene)cyclopentan-1-one [ No CAS ]
  • 20
  • [ 123-08-0 ]
  • [ 5270-94-0 ]
  • [ 491871-36-4 ]
YieldReaction ConditionsOperation in experiment
87% With potassium carbonate; In acetonitrile; at 80 - 85℃; Added 0.01mol (2.18g) 4,6- dimethoxy pyrimidine, 0.011mol (1.34g) hydroxybenzaldehyde with 125mL anhydrous acetonitrile was dissolved in 250mL three-necked flask, followed by the addition of carbonate drying small study potassium powder 1.38g (0.1mol), 80 ~ 85 heated to reflux, TLC monitoring of the reaction, the end of the reaction about 4-5 hours. The reaction liquid was cooled to room temperature, the solvent off most of the acetonitrile, 100mL of ethyl acetate was added to the system, the system was 50 mL water solids (potassium carbonate) dissolved in the organic phase washed with water and continue (50mL × 2), the combined aqueous phases, 20mL ethyl acetate three times. The combined organic phase was dried over anhydrous sodium sulfate. Filtered off the solvent to give a light brown oil. Silica gel column chromatography, eluent ethyl acetate: petroleum ether = 1/4, as a white solid. Yield 87%
  • 21
  • [ 121-33-5 ]
  • [ 5270-94-0 ]
  • 4-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxybenzaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With sodium carbonate; In N,N-dimethyl-formamide; at 120℃; Was added 0.01mol (1.86g) 4,6- dimethyl sulfoxide pyrimidine, 0.022mol (3.34g) 3- methoxy-4-hydroxybenzaldehyde in a 250mL three-necked flask, dissolved with 125mL dry DMF , followed by the addition of sodium carbonate powder drying fine grind 1.38g (0.1mol), 120 heated to reflux, TLC monitoring of the reaction, the end of the reaction is about 10 to 15 hours. Thereto were added 300mL of water, and then extracted three times with 100mL ethyl acetate and the combined organic phase was dried over anhydrous sodium sulfate. Filtered off the solvent to give a light brown oil. Silica gel column chromatography, eluent ethyl acetate: petroleum ether = 1/4, as a white solid. Yield 28%
  • 22
  • [ 15315-02-3 ]
  • [ 5270-94-0 ]
  • C9H7F7N2O2 [ No CAS ]
  • 23
  • [ 14353-88-9 ]
  • [ 5270-94-0 ]
  • 4,6-dimethoxy-5-(trifluoromethyl)pyrimidine [ No CAS ]
  • 24
  • [ 358-23-6 ]
  • [ 5270-94-0 ]
  • 4,6-dimethoxy-5-(trifluoromethyl)pyrimidine [ No CAS ]
  • 25
  • [ 2926-29-6 ]
  • [ 5270-94-0 ]
  • 4,6-dimethoxy-5-(trifluoromethyl)pyrimidine [ No CAS ]
 

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Technical Information

Categories

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