Structure of 37131-89-8
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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. : | 37131-89-8 |
Formula : | C5H2Cl2N2O2 |
M.W : | 192.99 |
SMILES Code : | ClC1=NC=C(C(=N1)Cl)C(=O)O |
MDL No. : | MFCD09999133 |
InChI Key : | IVIHUCXXDVVSBH-UHFFFAOYSA-N |
Pubchem ID : | 21941896 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 39.01 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.08 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.03 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.65 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.48 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.42 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.64 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.24 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.41 |
Solubility | 0.745 mg/ml ; 0.00386 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.59 |
Solubility | 0.498 mg/ml ; 0.00258 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.26 |
Solubility | 1.06 mg/ml ; 0.00547 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 |
-6.31 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 |
0.56 |
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) |
1.61 |
* 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 |
---|---|---|
65% | With N,N-diethylaniline; trichlorophosphate; In N,N-dimethyl-formamide; at 90℃; for 2.66667h;Under cold conditions; | To 10.0 g (64.06 mmol) of uracil-5-carboxylic acid (Aldrich Chemical Company) partially dissolved in 20 mL of DMF are added, under cold conditions, 59.7 mL (0.64 mol) of phosphorus oxychloride and 10.3 mL (64.7 mmol) of N,N-diethylaniline, and the mixture is then heated at 90° C. for 2 hours 40 minutes.After cooling to room temperature and evaporating off half the excess POCl3, the medium is poured onto ice and then extracted with ether.The ether phases are combined, dried over sodium sulfate, filtered and concentrated under vacuum. 8.1 g (41.97 mmol) of 2,4-dichloro-5-pyrimidinecarboxylic acid are obtained in a yield of 65percent. |
With N,N-dimethyl-aniline; trichlorophosphate; at 110℃; for 4h;Cooling with ice; | To a 25 ml three-necked flask was added uracil-5-carboxylic acid (1 g, 6.4 mmol)N, N-dimethylaniline (1.09 g, 9. 0 mmol) was added dropwise to a solution of phosphorus oxychloride (9.83 g, 64. lmmol) under ice-cooling.After the dropwise addition, the ice bath was heated to 110 ° C for 4 hours. After the reaction solution was cooled, it was slowly added to the ice water for quenching.The aqueous phase was extracted with ethyl acetate and the organic phase was washed twice with water, once with saturated brine, dried over anhydrous sodium sulfate and concentrated to give 960 mg of crude oil as an oil, 2,4-dichloro-5-pyrimidinecarboxylic acid Purification is used directly for the next step |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With water; In diethyl ether; at 35℃; for 1h; | To a solution of 9 g (42.8 mmol) of 2,4-dichloro-5-pyrimidinecarboxylic acid chloride (Manchester Organics Limited) in 60 mL of ether are added 10 mL of water and the reaction mixture is stirred vigorously at 35 C. for 1 hour. After addition of ether and separation of the phases by settling, the organic phase is dried over Na2SO4, filtered and concentrated under vacuum. 7.7 g of a colourless oil that solidifies rapidly in air, and which is used immediately in the following step, are obtained. Yield=93%. |
With water; In tetrahydrofuran; at 20℃; for 0.83h; | To a solution of the <strong>[2972-52-3]2,4-dichloropyrimidine-5-carbonyl chloride</strong> (24 mmol) in THF (24 ml) is added H2O (0.64 ml) at room temperature. The reaction mixture is stirred at room temperature for 0.83 h and then diluted with HaO. The mixture is extracted with AcOEt. The organic extracts are washed with brine, dried over Na2SO4, filtered, and concentrated in vacua to give the crude titled compound; 1H NMR (CDCI3) 5 6.80 (brs, 1H), 9.18 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With thionyl chloride; at 80℃; for 4h; | To a 50 ml three-necked flask was added successively the crude product (0.6 g, 3.1 mmol) in the previous step,Thionyl chloride (10 ml) and heated to 80 C for 4 hours.Concentrated to dryness under reduced pressure to give 0.6 g of 2,4-dichloro-5-pyrimidinecarboxylic acid chloride in a yield of 90% |
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 1h; | To a solution of 2,4-dichloropyrimidine-5-carbonyl chloride(100 mg, 0.47 mmol) in DCM (10 mL) added ammonium thiocyanate(54 mg, 0.71 mmol, 1.5 equiv) dropwise under stirring. A dropof PEG-400 was added to the suspension, it was then stirred atroom temperature for 20 min. After consumption of the startingmaterial, 1-(cyclohexylmethyl)piperazine (86 mg, 0.47 mmol) wasadded. It was then stirred for 1 h at room temperature. The reactionmixture was then diluted with water (30 mL) and extracted withDCM (20 mL 3). The organic extracts were dried over anhydrousMgSO4 and concentrated under reduced pressure. The residue waspurified by column chromatography on silica gel to afford compoundB02 as a white solid (159 mg, yield 89%): EtOAc-PET (1:3,Rf 0.27); 1H NMR (400 MHz, CDCl3) d 9.36 (s, 1H), 4.17 (br, 2H),3.74 (br, 2H), 2.57 (s, 4H), 2.21 (s, 2H), 1.81e1.73 (m, 6H), 1.51 (br,1H), 1.35e1.23 (m, 2H), 0.92e0.88 (m, 2H); 13C NMR (151 MHz,CDCl3) d 167.3, 166.6, 162.3, 161.0, 160.0, 115.9, 65.0, 53.0, 52.8, 47.0,46.6, 35.0, 31.6, 26.7, 26.0; HRMS (CI) m/z [MH] calcd forC17H23ClN5OS, 380.1306; found, 380.1317. | |
With thionyl chloride;Reflux; | To 2,4-dichloropyrimidine-5-carboxylic acid (1 g, 5.1817 mmol) was added thionyl chloride (13.120 g, 8 mL, 110.28 mmol) and the resulting suspension was refluxed overnight. The reaction mixture was concentrated under reduced pressure to provide 2,4- dichloropyrimidine-5-carbonyl chloride (1.31 g, 114%) 1H NMR (400 MHz, CDCl3) d 9.26 (s, 1H). |
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