Structure of 302964-02-9
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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. : | 302964-02-9 |
Formula : | C9H12N2O4S |
M.W : | 244.27 |
SMILES Code : | O=C(C1=CN=C(NC(OC(C)(C)C)=O)S1)O |
MDL No. : | MFCD06796614 |
InChI Key : | QNFLEDLPOVONCN-UHFFFAOYSA-N |
Pubchem ID : | 22271442 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H317 |
Precautionary Statements: | P261-P280 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.44 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 59.32 |
TPSA ? Topological Polar Surface Area: Calculated from |
116.76 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.63 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.71 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.33 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.27 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.39 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.33 |
Solubility | 1.13 mg/ml ; 0.00465 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.78 |
Solubility | 0.0408 mg/ml ; 0.000167 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.63 |
Solubility | 5.78 mg/ml ; 0.0237 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 |
-6.58 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 |
0.0 |
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) |
2.96 |
* 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 |
---|---|---|
96% | With sodium hydroxide; In tetrahydrofuran; methanol; water; at 20℃; for 24h; | [0405] A stirred solution of ethyl-2-tert-butoxycarbonyloxyamino-4-methyl-thiazole-5-carboxylate (1.1 g, 4.2 mmol) in tetrahydrofuran-methanol (80 mL, 1:1) was treated with a 6N aq. NaOH solution (20 mL, 120 mmol). The mixture was stirred at rt for 24 h. Most of THF and methanol were removed by distillation under reduced pressure and the aq. Solution was acidified with 6 N aq. HCl solution (22 mL). The precipitated solid was filtered, washed with water and ether, air dried followed by drying in vacuo to obtain the title acid (940 mg, 96%) as an off-white solid. |
With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; at 0 - 20℃; for 1h; | To an cooled (0 C) dichloromethane (4 mL) solution of 2-[(tert- butoxycarbonyl)amino]-l,3-thiazole-5-carboxylic acid (0.30 g) was added a solution of oxalyl chloride (0.13 mL) in dichloromethane (1 mL). One drop of N,N- dimethylformamide was added and the mixture stirred at room temperature for 1 hour. The reaction mixture was concentrated and the residue dissolved in acetonitrile (5 mL). To the cooled (0 C) acetonitrile solution, a 2 M solution of (trimethylsilyl)diazomethane in tiexanes (1.23 mL) was added and the mixture stirred at 0 C for 1 hour. To the reaction mixture, a solution of 33 wt. % hydrogen bromide in acetic acid (0.20 mL) was added and the mixture stirred at 0 C for a further 20 minutes. A saturated aqueous solution of sodium hydrogen carbonate ( 0 mL) was added followed by extraction with ethyl acetate. The combined organic layers were washed with brine, dried and concentrated to give the crude title compound having the following physical properties (0.37 g). LC MS fR 1.92 minutes; MS (ES+) m/z 265 and 267 (M-C(CH3)3+H) a. | |
With oxalyl dichloride; In dichloromethane; | [00106] Compound 8 was made using by adapfing the synthesisdsdosed n J.Med.Chem. 2006, 6819. Synthesis of amde 5 was accomphshedn two steps, starting from compound 1. Compound I was converted to acidchorde 2 using oxay chorde n dchoromethane (DCM). Formafion of theacd chorde was confirmed by quenching an aquot n methano (MeOH);LCMS anayss ndcated the presence of the corresponding methy? ester 3 n>90%. Add Won of 2 to a mixture of excess anWne 4 and dsopropy ethyamne(DPEA) gave good conversion to amine 5. After fHtehng the sohds off thisafforded 1.15 g (40%) amde 5 n high purIty. Remova of the Boc-group using tr[fluoroacefic acid (TFA) gave good conversion to amine 6. Amine 6 was converted to compound 8 n the presence of compound 7 and sodium t-butoxde (NaOBu-t). |
With thionyl chloride; N,N-dimethyl-formamide; In tetrahydrofuran; dichloromethane; at 25 - 30℃; | Into a clean and dry 1 L 4-neck round bottom flask connected to a mechanical stirrer, condenser, thermometer socket is charged with 2-tert-butoxy-carbonylaminothiazole-5-carboxylic acid (3) (25.0 g), THF (1 L) and DMF (1 mL) at 25-30 C under stirring. Charged thionyl chloride (22.5 mL of thionyl chloride dissolved in 125 mL of dichloromethane) to the mass at 25-30 C. Maintained the reaction mass at 25-30 C for 4-6 h and after TLC compliance, distilled-off solvent completely under plant vacuum at the temperature not crossing 50 C. Charged THF (125 mL) to the reaction mass, stirring the mass for 10-15 min and distilled-off solvent completely under plant vacuum at the temperature not crossing 40 C. Charged 125 mL of dichloromethane to the reaction mass, stirring the mass for 10-15 min and distilled-off solvent completely under plant vacuum at the temperature not crossing 40 C to furnish 27-28 g of crude compound. | |
With thionyl chloride; In tetrahydrofuran; dichloromethane; N,N-dimethyl-formamide; at 25 - 30℃; | Into a clean and dry 1.0. L 4-neck RB charged 2- tert-butoxycarbonylamino- thiazole-5-carboxylic acid(25gm),and THF(lltr, Lot-I) and DMF(10 ml) at (0075) temperature 25-30C under stirring. Charged thionyl chloride (22.5 ml, dissolved (0076) in 125ml of dichloromethane-Lot-I) to the mass at temperature 25-30C, (0077) maintained the mass at temperature 25-30C for 4-6hrs., after completion of the (0078) reaction, distilled-off solvent completely under plant vacuum at temperature not (0079) crossing 50C, charged THF (125ml, Lot-II) to reaction mass.Stirr the mass for (0080) 10-15 min. Distilled-off solvent completely under plant vacuum at temperature not crossing 40C, charged dichloromethane (125ml, Lot-II) to reaction mass. (0081) Stirred the mass for 10-15 min.Distilled-off solvent completely under plant (0082) vacuum at temperature not crossing 40C. Distilled-off solvent completely under (0083) plant vacuum at temperature not crossing 60C. Crude acid chloride is directly (0084) taken to next stage in-situ. (0085) Weight: 27 gm |
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