Structure of 598-50-5
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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. : | 598-50-5 |
Formula : | C2H6N2O |
M.W : | 74.08 |
SMILES Code : | O=C(N)NC |
MDL No. : | MFCD00007950 |
InChI Key : | XGEGHDBEHXKFPX-UHFFFAOYSA-N |
Pubchem ID : | 11719 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 5 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 17.83 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.69 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-1.4 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.72 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.96 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.22 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.72 |
Log S (ESOL):? ESOL: Topological method implemented from |
0.65 |
Solubility | 330.0 mg/ml ; 4.45 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.74 |
Solubility | 411.0 mg/ml ; 5.55 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
0.23 |
Solubility | 124.0 mg/ml ; 1.68 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 |
No |
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 |
-7.75 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 |
2.0 |
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) |
1.0 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; | EXAMPLE 9 STR24 A mixture of alpha-trifluoromethylacrylic acid (700 mg; 5.0 mmoles) and methylurea (407 mg; 5.5 mmoles) in DMF (3 ml) was heated at 90 C. with stirring for 4 hours. DMF was evaporated under reduced pressure. The residue was purified by a column chromatography on silica gel to give 118 mg (yield 12%) of 1-methyl-5-trifluoromethyl-5,6-dihydrouracil (OF-3), 20 mg (yield: 2%) of 3-methyl-5-trifluoromethyl-5,6-dihydrouracil and 706 mg (yield: 66%) of 1-(2-hydroxycarbonyl-3,3,3-trifluoropropyl)-3-methylurea. 1-(2-Hydroxycarbonyl-3,3,3-trifluoropropyl)-3-methylurea: m.p.: 149.5-150.5 C. Mass spectrum: m/e (relative intensity) M+ 214(9), 30 (100). IR (KBr): 3430, 3400 cm-1 (nuN--H), 3600-2200 cm-1 (nuO--H). 1740, 1725, 1610 cm-1 (nuc=o). 1 H NMR (CD3 COCD3:TMS): delta2.70(s, 3H), 3.3-3.8(m, 3H), 5.9(bs, 1H). 6.1(bs, 1H), 10.7(bs, 1H). 19 F NMR (CD3 COCD3:CFCl3): delta-66.1(m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | at 100℃; for 18h;Inert atmosphere; | Step 1 : 1 ,6-dimethylpyrimidine-2,4(l H,3H)-dioneA solution of 1-methylurea (30 g, 0.356 mol) in 4-methyleneoxetan-2-one (26.4 g, 0.356 mol) was heated at 100C for 18 h, cooled to RT then diluted with MeOH (50 mL). The reaction was filtered and the filtered solid was washed with MeOH (20 mL) and dried to give 1,6- dimethylpyrimidine-2,4(lH,3H)-dione (9 g, 8% yield) as a white solid. ]H NMR (CDClj) 6: 8.33 (s, 1H), 5.58 (s, 1H), 3.38 (s, 3H), 2.26 (s, 3H). LCMS: MH+ 141 and TR = 0.368 min. Used without further purification. |
14% | In acetic acid; at 120℃; for 12h; | 4-Methyleneaxetan-2-one (8.0 g, 95 mmol) and N-methylurea (5.0 g, 68 mmol) were dissolved in acetic acid (50 ml), followed by stirring at 120 C. for 12 hours. The solvent was removed under reduced pressure. To the obtained residue, ethyl acetate (50 ml) was added, followed by stirring for 30 minutes. After the precipitated solid was filtered, purification was conducted by reversed-phase HPLC (H2O containing 0.1% FTA/CH3CN system) to obtain the title compound (1.3 g, 14%). [0618] 1H NMR (400 MHz, CD3OD): δ 5.59 (s, 1H), 3.39 (s, 3H), 2.32 (s, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene;tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; at 100℃; for 2h; | Example 14N-hydroxy-3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide; Compound I-286 Step 1: methyl 3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate Intermediate-5To a solution of <strong>[18643-86-2]dimethyl 2-bromoterephthalate</strong> (0.25 g, 0.92 mmol) and methylurea (88.2 mg, 1.19 mmol) in 1,4-dioxane (7 mL) was added cesium carbonate (0.60 g, 1.83 mmol). 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (53.0 mg, 0.092 mmol) was then added followed by tris(dibenzylideneacetone)dipalladium (42 mg, 0.046 mmol). The reaction mixture was heated to 100 C. and stirred for 2 d. The mixture was then cooled to rt and concentrated. Water was added and the remaining solid was filtered. The collected solid was then washed with DCM (3×) to afford methyl 3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate (0.15 g, 70%). LC-MS: (FA) ES+235; 1H NMR (400 MHz, DMSO) δ 11.63 (s, 1H), 8.05 (d, J=8.2 Hz, 1H), 7.77 (d, J=1.4 Hz, 1H), 7.71 (dd, J=8.2, 1.5 Hz, 1H), 3.89 (s, 3H), 3.26 (s, 3H). |
58.3% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 120℃; for 16h; | To a solution of <strong>[18643-86-2]dimethyl 2-bromoterephthalate</strong> (3.00 g, 10.99 mmol) and 1-methylurea (1.06 g, 14.28 mmol) in 1,4-dioxane (10.0 mL) was added cesium carbonate (7.16 g, 21.97 mmol), xantphos (0.64 g, 1.099 mmol) and tris(dibenzylideneacetone)dipalladium(0) (1.00 g, 1.099 mmol). The reaction mixture was heated to 120C for 16 h. The reaction mixture was then cooled to room temperature and concentrated to afford crude solid. To the crude solid add 60.0 mL dichloromethane and stirred it for 5 minutes. Filtered this reaction mixture to get crude solid which was purified by column chromatography using eluent 0-10% of methanol in dichloromethane to afford the titled compound methyl 3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate 1.5 g, 58.3 % yield as a light yellow solid. MS (ES+) m/z = 235.27 (M+1). 1H NMR (400 MHz, DMSO-d6) δ 11.63 (s, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.80 - 7.67 (m, 2H), 3.90 (s, 3H), 3.27 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15.2% | With hydrogenchloride; In ethanol; water; for 72.0h;Reflux; | [00156] A mixture of 1,2-diphenylethanone (400 mg, 2.04 mmol), 3-ethoxy-4- hydroxy- 5 -nitrobenzaldehyde (430 mg, 2.04 mmol), and 1-methylurea (454 mg, 6.12 mmol) in anhydrous EtOH was added concentrated HC1 (204 mg, 2.04 mmol), and the reaction mixture was refluxed for 3 days. When TLC (EtOAc:MeOH=10: l) showed that the starting materials were consumed, the reaction mixture was concentrated, and purified by preparative HPLC to afford Compound 11 as a yellow solid (138 mg, yield: 15.2%). 1H NMR (DMSO- d6 400 MHz TMS): delta 10.25 (s, 1H), 7.68 (d, J = 2.8 Hz, 1H), 7.45 (s, 1H), 7.20-7.28 (m, 3H), 7.15-7.20 (m, 3H), 6.85-6.95 (m, 3H), 6.70 (d, J = 6.4 Hz, 1H), 5.00 (d, J = 2.4 Hz, 1H), 4.02 (m, 2H), 2.60 (s, 3H), 1.30 (t, J = 7.0 Hz, 3H); MS (ESI): m/z 446.2 [M+l]+. |