Structure of 21075-86-5
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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. : | 21075-86-5 |
Formula : | C8H16N2O2 |
M.W : | 172.22 |
SMILES Code : | NN(C(OC(C)(C)C)=O)CC=C |
MDL No. : | MFCD18447709 |
InChI Key : | ZTWGIZOCAXOUOE-UHFFFAOYSA-N |
Pubchem ID : | 10535205 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H227-H302 |
Precautionary Statements: | P280 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.62 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 47.41 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.56 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.24 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.01 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.28 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.34 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.32 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.21 |
Solubility | 10.5 mg/ml ; 0.0611 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.77 |
Solubility | 2.95 mg/ml ; 0.0171 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.6 |
Solubility | 43.0 mg/ml ; 0.249 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 |
-6.63 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 |
3.0 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) |
2.45 |
* 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 |
---|---|---|
51% | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; for 72h;Reflux; | DIPEA (20.8 ml, 120 mmol) and allyl hydrazine 5 (8.23 g, 47.8 mmol) were added to a solution of ethyl 4-chloro-2-methylthio- 5-pyrimidinecarboxylate (6; 1 1.1 g, 47.8 mmol) in THF (150 ml). The reaction mixture was heated at reflux for 72 h, before being concentrated in vacuo. Et20 (50 ml) was added to the residue, and the resultant precipitate was collected by filtration. The filtrate was evaporated to dryness, and the residue was cooled in an ice bath, after which TFA (40 ml) was added. The resultant solution was stirred at RT for 1 h, followed by 70 C for 1 h. The solvent was removed in vacuo and the residue was dissolved in EtOH (50 ml) and cooled in an ice bath, after which 6M NaOH (75 ml) was added. The resultant solution was stirred at RT for 15 min, before 32 being acidified via the addition of cone. HCI (40 ml). The orange solution was evaporated to dryness and the resultant residue was partitioned between chloroform (100 ml) and water (100 ml), and the organic phase was washed with brine (50 ml), dried (Mg2S04), concentrated in vacuo, and triturated with hexanes. The solid precipitate was washed with EtOH and Et20, before being dried under vacuum to give the target compound as a yellow solid (5.44 g, 24.5 mmol, 51 %). Rf 0.45 (9:1 DCM:MeOH); M.p. 125- 128 C; IR (cm-1 ) 3032, 2979, 2926, 2659, 1656, 161 5, 1 566, 1 514; 1 H NMR (400 M Hz, DMSO-d6)2.53 (3H, s, -SCH3), 4.38 (2H, dapp, J = 5.2 Hz, N2-CH2), 5.06-5.20 (2H, m, allyl C-Hcis/trans), 5.87 (1 H, ddt, J = 17.2, 10.5, 5.3 Hz, alkene C-H), 8.67 (1 H, s, H-4), 12.65 (1 H, -1 ); MS [M + H] + m/z 223.1. |
260 mL of N,N-diisopropylethylamine and 106 g of the hydrazine obtained in the above 1 were added to tetrahydrofuran (1.5 L) solution of 142 g of ethyl 4-chloro-2-(methylthio)pyridine-5-carboxylate, and stirred with heating under reflux for 18 hours. After cooled to room temperature, the reaction solution was evaporated under reduced pressure, and 500 mL of diethyl ether was added to the residue, and the precipitated solid was separated through filtration. The filtrate was evaporated under reduced pressure, the residue was cooled in an ice bath, 400 mL of trifluoroacetic acid was gradually added thereto, and stirred at room temperature for 1 hour and then at 70 C. for 1 hour. The reaction solution was evaporated under reduced pressure, 500 mL of ethanol was added thereto and cooled in an ice bath, and 1.0 L of 6 N sodium hydroxide solution was added thereto and stirred at room temperature for 15 minutes. Cooled in an ice bath, the reaction solution was made acidic with 400 mL of concentrated hydrochloric acid, and then evaporated under reduced pressure. The residue was partitioned in chloroform and water, and the chloroform layer was extracted, washed with saturated saline water, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the formed yellow solid was taken out through filtration, washed with ethanol and diethyl ether, and dried to obtain 99.1 g of the entitled compound as a yellow solid.1H-NMR (400 MHz, DMSO-d6) ?: 8.66 (1.0H, brs), 5.83 (1.0H, ddt, J=17.1, 9.8, 5.4 Hz), 5.13 (1.0H, d, J=9.8 Hz), 5.06 (1.0H, d, J=17.1 Hz), 4.34 (2.0H, d, J=5.4 Hz), 2.51 (3.0H, s).ESI-MS Found: m/z[M+H]+ 223.3. | ||
2) Production of 2-allyl-6-(methylthio)-l ,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one:260 mL of N,N-diisopropylethylamine and 106 g of the hydrazine obtained in the above 1 were added to tetrahydrofuran (1.5 L) solution of 142 g of ethyl 4-chloro-2- (methylthio)pyridine-5-carboxylate, and stirred with heating under reflux for 18 hours. After cooled to room temperature, the reaction solution was evaporated under reduced pressure, and 500 mL of diethyl ether was added to the residue, and the precipitated solid was separated through filtration. The filtrate was evaporated under reduced pressure, the residue was cooled in an ice bath, 400 mL of trifluoroacetic acid was gradually added thereto, and stirred at room temperature for 1 hour and then at 70C for 1 hour. The reaction solution was evaporated under reduced pressure, 500 mL of ethanol was added thereto and cooled in an ice bath, and 1.0 L of 6 N sodium hydroxide solution was added thereto and stirred at room temperature for 15 minutes. Cooled in an ice bath, the reaction solution was made acidic with 400 mL of concentrated hydrochloric acid, and then evaporated under reduced pressure. The residue was partitioned in chloroform and water, and the chloroform layer was extracted, washed with saturated saline water, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the formed yellow solid was taken out through filtration, washed with ethanol and diethyl ether, and dried to obtain 99.1 g of the entitled compound as a yellow solid. iH-NMR (400 MHz, DMSO-d6) delta: 8.66 (1.0H, brs), 5.83 (1.0H, ddt, J=17.1, 9.8, 5.4 Hz), 5.13(l.OH, d, J=9.8 Hz), 5.06 (1.0H, d, J=I 7.1 Hz), 4.34 (2.0H, d, J=5.4 Hz), 2.51 (3.0H, s). ESI-MS Found: m/z[M+H]+ 223.3. |
260 mL of N,N-diisopropylethylamine and 106 g of the hydrazine obtained in the above 1 were added to tetrahydrofuran (1.5 L) solution of 142 g of ethyl 4-chloro-2- (methylthio)pyridine-5-carboxylate, and stirred with heating under reflux for 18 hours. After cooled to room temperature, the reaction solution was evaporated under reduced pressure, and 500 mL of diethyl ether was added to the residue, and the precipitated solid was separated through filtration. (0207) The filtrate was evaporated under reduced pressure, the residue was cooled in an ice bath, 400 mL of trifluoroacetic acid was gradually added thereto, and stirred at room temperature for 1 hour and then at 70C for 1 hour |
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