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Structure of Citraconic anhydride
CAS No.: 616-02-4
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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. : | 616-02-4 |
Formula : | C5H4O3 |
M.W : | 112.08 |
SMILES Code : | CC1=CC(=O)OC1=O |
MDL No. : | MFCD00005522 |
InChI Key : | AYKYXWQEBUNJCN-UHFFFAOYSA-N |
Pubchem ID : | 12012 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H303-H311-H314-H317-H334 |
Precautionary Statements: | P264-P270-P272-P280-P285-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P405-P501 |
Class: | 8(6.1) |
UN#: | 2922 |
Packing Group: | Ⅲ |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 25.05 |
TPSA ? Topological Polar Surface Area: Calculated from |
43.37 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.94 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.25 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.02 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.23 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.98 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.48 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.69 |
Solubility | 22.8 mg/ml ; 0.203 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.72 |
Solubility | 21.3 mg/ml ; 0.19 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.58 |
Solubility | 29.1 mg/ml ; 0.26 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 |
-6.81 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 |
2.0 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) |
1.96 |
* 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 |
---|---|---|
70% | With 1,1,1,3,3,3-hexamethyl-disilazane; In N,N-dimethyl-formamide; at 100℃; for 1h; | To a solution of citraconic anhydride (25) (12.0 g, 107 mmol) in DMF (100 mL) at 100 C hexamethyldisilazane (34.2 mL, 160 mmol) was added. The mixture was stirred at 100 C for 1 h, then it was cooled to room temperature. The solvent was evaporated under reduced pressure. The crude product was recrystallized from a mixture of hexane and ethyl acetate to give the title compound 26 as a white crystalline solid (8.33 g, 70%), mp 104-105 C (lit.: 104-105 C) [3]; Rf (DCM:MeOH 10:1) 0.71; nmax (KBr) 3271, 3098, 2674, 1844, 1778, 1764, 1712, 1634, 1342, 1284, 1175, 1090 cm_1; 1H NMR (500 MHz; DMSO-d6) d (ppm) 1.94 (3H; d; J 1.8 Hz; C(3)-CH3); 6.50 (1H; q; J 1.8 Hz; H-4); 10.72 (1H; br s; NH-1); 13C NMR (126 MHz; DMSO-d6) d (ppm) 10.2 (C(3)-CH3); 128.0 (C-4); 145.9 (C-3); 172.2 (C-5); 173.1 (C-2); HRMS: M 111.0311 (C5H5O2N; delta _8.1 ppm); HR-EI-MS (rel. int. %): 111(100); 83(8); 68(39). |
40% | With 1,1,1,3,3,3-hexamethyl-disilazane; In methanol; N,N-dimethyl-formamide; at 0 - 20℃; for 20.3333h; | Stage 1: 3-methylpyrrole-2,5-dione A solution of hexamethyldisilazane (80.7 g, 104.8 ml, 500 mmol) in methanol was added dropwise to a solution of citraconic anhydride (5.60 g, 4.49 ml, 50 mmol) in N,N-dimethylformamide (170 ml) at 0 C. The reaction solution was stirred at room temperature for 20 h, thereafter methanol (100 ml) was added and the mixture was stirred for a further 20 min. The solvent was concentrated in vacuo and the residue was taken up in a mixture of ethyl acetate/water (150 ml:50 ml). The organic phase was separated off, washed with water (2*50 ml), sodium bicarbonate solution (50 ml) and with water again (50 ml) and then dried with sodium sulfate. The solvent was concentrated and the residue was dried in vacuo. Yield: 2.30 g (40%), white solid Melting point: 100-102 C. [lit. 101-104 C. (K. R. Shah, C. DeWitt Blanton, J. Org. Chem. 1982, 47, 502)]. |
32% | With urea; In sulfolane; at 180℃; for 1h;Product distribution / selectivity; | 25 g (0.219 mol) of 2-methyl succinic anhydride were heated in 37.5 g of sulfolane to a reaction temperature of 180 C. After the reaction temperature was achieved 18.95 g (0.32 mol) of urea were spread in and stirring was continued for 1 h at the reaction temperature under flushing with N2. Following cooling, the reaction mixture was first added with 2-propanol and then with MTBE. 6.5 g of 2-methyl succinic imide (32% of the theoretical yield) were obtained |
20% | With urea; In diethyleneglycol diethylether; at 180℃;Product distribution / selectivity; | EXAMPLE 25 In a manner analogous to that of Example 24, diethyleneglycol diethylether was used as the solvent at 180 C. After cooling, first MTBE was added. From the resulting oil 2-methyl succinic imide was obtained in a yield of 20% by recrystallization from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With acetic acid; In toluene; for 1h;Inert atmosphere; Reflux; | In caseIn a separable flask,50 g (0.234 mol) of <strong>[84-67-3]2,2'-dimethylbiphenyl-4,4'-diamine</strong> (m-TB, manufactured by Wakayama Seika Industry Co., Ltd.)71 g (1.18 mol) of acetic acid and 120 g of toluene were charged and dissolved while heating and stirring at 50 ° C. while introducing nitrogen. 52.8 g (0.472 mol) of citraconic anhydride was added dropwise, and gradually heated while removing generated water outside the system,The reaction was carried out under reflux for 1 hour.After purifying the reaction product by reprecipitation, 90 g of a white crystal bismaleimide compound (e-1) was obtained. Yield 96percent. It was confirmed that the amine equivalent was 100,000 or more and almost all of the amino groups were reacted. |
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