Structure of 5270-94-0
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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. : | 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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
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 |
44.24 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.57 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.96 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.49 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.11 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.85 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.75 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.63 |
Solubility | 3.32 mg/ml ; 0.0237 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.48 |
Solubility | 4.68 mg/ml ; 0.0334 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.88 |
Solubility | 1.84 mg/ml ; 0.0132 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 |
-6.47 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) |
1.72 |
* 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 |
---|---|---|
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). |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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% |
Yield | Reaction Conditions | Operation 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% |
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