Structure of 955369-56-9
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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. : | 955369-56-9 |
Formula : | C17H19N5O2S |
M.W : | 357.43 |
SMILES Code : | CSC1=NC2=C(C=N1)C(=O)N(CC=C)N2C1=NC(=CC=C1)C(C)(C)O |
MDL No. : | MFCD19443207 |
InChI Key : | CTAHQYLRFXBFKB-UHFFFAOYSA-N |
Pubchem ID : | 67170189 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 25 |
Num. arom. heavy atoms | 15 |
Fraction Csp3 | 0.29 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 98.67 |
TPSA ? Topological Polar Surface Area: Calculated from |
111.13 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.02 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.14 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.8 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.05 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.2 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.52 |
Solubility | 0.108 mg/ml ; 0.000303 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.11 |
Solubility | 0.028 mg/ml ; 0.0000784 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.12 |
Solubility | 0.0271 mg/ml ; 0.0000759 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
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 |
-6.96 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 |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 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) |
3.34 |
* 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 |
---|---|---|
74% | With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 80℃; | Step-3: Synthesis of 2-allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-2-pyridyl]-6-methylsulfanyl-pyrazolo[3,4-d]pyrimidin-3-one To a stirred solution of 2-allyl-6-methylsulfanyl-1H-pyrazolo[3,4-d]pyrimidin-3-one (200 mg, 0.90 mmol, 1.0 eq) and <strong>[638218-78-7]2-(6-bromo-2-pyridyl)propan-2-ol</strong> (233 mg, 1.08 mmol, 1.20 eq) in 10 mL of dioxane were added copper iodide (171 mg, 0.90 mmol, 1.0 eq), potassium carbonate (186 mg, 1.35 mmol, 1.5 eq) and N,N'-dimethylethylenediamine (87 mg, 0.99 mmol, 1.1 eq) and stirred at 80 C. for overnight. After completion of reaction, solvent was removed under reduced pressure; residue was diluted with water and extracted with ethyl acetate (30 mL*3). Combined organic layer was washed with brine solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford crude product, which was purified by flash chromatography to afford 240 mg (74%) of 2-allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-2-pyridyl]-6-methylsulfanyl-pyrazolo[3,4-d]pyrimidin-3-one. |
47% | With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 95℃; | Into a lOOO-mL 3-necked round-bottom flask, was placed 6-(methylsulfanyl)-2-(prop-2-en-l-yl)-lH,2H,3H- pyrazolo[3,4-d]pyrimidin-3-one (20 g, 89.98 mmol, 1.00 equiv), <strong>[638218-78-7]2-(6-bromopyridin-2- yl)propan-2-ol</strong> (24 g, 111.07 mmol, 1.23 equiv), 1,4-dioxane (500 mL), iodocopper (17.1 g, 89.79 mmol, 1.0 equiv), K2C03 (17.1 g, 122.83 mmol, 1.37 equiv). This was followed by the addition of methyl [2-(methylamino) ethyl] amine (10.8 mL) dropwise with stirring. The resulting solution was stirred overnight at 95C in an oil bath. The resulting mixture was cooled to room temperature. The mixture was then quenched by the addition of 100 mL of water. The resulting mixture was concentrated under vacuum. The residue was extracted with 3x500 mL of ethyl acetate and the organic layers combined. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5- 1:3). This resulted in 15 g (47%) of l-[6-(2-hydroxypropan-2-yl) pyridin-2-yl]-6-(methylsulfanyl)-2-(prop-2-en-l-yl)-lH,2H,3H- pyrazolo[3,4-d]pyrimidin-3-one as a white solid. LC-MS(ES, m/z) M+l=358 |
With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 95℃; | General procedure: 2.4 mL of N,N?-dimethylethylenediamine was added to 1,4-dioxane (50 mL) solution of 4.44 g of 2-allyl-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one, 3.80 g of copper(I) iodide, 5.33 g of 2-iodopyridine and 3.80 g of potassium carbonate, and stirred overnight at 95 C. The reaction liquid was cooled, aqueous ammonia was added thereto and extracted with ethyl acetate, washed with saturated saline water and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and crystallized with ethyl acetate to obtain the entitled compound as a white solid Step 2) Production of 2-allyl-1-[6-(1-hydroxy-1-methylethyl)-2-pyridinyl]-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one The entitled compound was obtained in the same manner as in Preparative Example 1-1, for which, however, the compound obtained in the above reaction was used in place of 2-iodopyridine used in Preparative Example 1-1. 1H-NMR (400 MHz, CDCl3) delta: 8.95 (1H, s), 7.91 (1H, t, J=8.0 Hz), 7.76 (1H, d, J=7.3 Hz), 7.40 (1H, dd, J=7.8, 1.0 Hz), 5.70 (1H, ddt, J=17.1, 10.2, 6.3 Hz), 5.06 (1H, dd, J=10.2, 1.0 Hz), 4.93 (1H, dd, J=17.1, 1.2 Hz), 4.81 (2H, d, J=6.3 Hz), 2.59 (4H, s), 1.59 (6H, s). ESI-MS Found: m/z[M+H]+:358. |
With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 80 - 95℃; for 18h; | General method for the preparation of pyridyl pyrazolopyrimidinones (9a-c). Nu,Nu'- Dimethylethylenediamine (4.47 mmol) was added to a solution of pyrazolopyrimidine 7 (2.25 mmol), bromopyridine (8a-c; 2.93 mmol), copper iodide (2.25 mmol) and K2C03 (3.1 5 mmol) in 1 ,4-dioxane (5 ml) at 80 C. The resultant suspension was heated at 95 C for 18 h, over which time a colour change of orange to dark green occurred. The reaction mixture was cooled to RT and diluted with NH40H (10 ml) before being extracted with EtOAc (2 x 20 ml). The combined organic extracts were washed with brine (20 ml), dried 33 (MgS04) and evaporated to dryness. The crude material was purified via silica gel chromatography (19:1 DCM:MeOH) to afford the target pyridyl pyrazolopyrimidinones (69-84%). 2-Allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(methylthio)-1,2-dihydro-3H- pyrazolo[3,4- d]pyrimidin-3-one (9a). Rf 0.63 (9:1 DCM:MeOH); M.p.108-111 C; IR (cm-1) 3337, 3081, 2966, 2924, 1663, 1601, 1559; 1H NMR(400 MHz, CDCI3) 1.61 (6H, s, C(CH3)2), 2.61 (3H, s, S-CH3), 3.77 (1H, s, -OH), 4.82 (2H, dapp, J = 5.9 Hz, N2-CH2), 4.95 (1H, dapp, J = 16.9 Hz, allyl C-Htrans), 5.08 (1H, dapp, J = 10.3 Hz, allyl C-Hcis), 5.72 (1H, dd = 16.9, 10.3, 5.9 Hz, allyl C-H), 7.42 (1H, d, J = 7.7 Hz, H-5'), 7.78 (1H, d,J = 8.0 Hz, H-3'), 7.93 (1H, dd,J = 8.0, 7.7 Hz, H-4'), 8.96 (1H, s, H-4); 13C NMR(125 MHz, CDCI3) 14.5 (SCH3), 30.5 (C(CH3)2), 47.5 (N2-CH2), 72.5 (C(CH3)2), 116.4 (Ar-C), 116.6 (Ar-C), 119.3 (allyl-CH2), 131.2, 139.2, 147.0 (Ar-C), 154.3 (Ar-C), 159.2 (C=0), 161.0 (Ar-C), 166.1 (Ar-C), 177.0 (Ar-C); MS [M + H]+ m/z 359.3. | |
1.8 g | With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 100℃; for 12h;Inert atmosphere; | Compound N1, N2-dimethylethane-1,2-diamine (872 mg) was added to compound S-4 (2g), and 2- (6-bromopyridin-2-yl) propan-2-ol ( 2.3 g), CuI (1.7 g) and potassium carbonate (2.5 g) in 1,4-dioxane (25 mL). Heat to 100 C under nitrogen and stir for 12 hours. After cooling to room temperature, a saturated ammonium chloride solution (50 mL) was added to the reaction system, and extracted with DCM. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (DCM / MeOH, 45: 1, v / v) to give the target product Int-1 (1.8 g) as a pale yellow solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.6mg | To a toluene solution (5 mL) of compound Int-1 (100 mg), m-CPBA (146 mg) was added and stirred at room temperature overnight to obtain a solution A. NaH (56 mg) was added to a DMF (5 mL) solution in which Compound A-31 (59 mg) was dissolved, and stirred at room temperature for 30 minutes to obtain a mixture B. Then A was slowly added to B and stirred overnight at room temperature. The reaction solution was poured into a saturated ammonium chloride solution, a white solid was precipitated, and the filter cake was purified by thin layer chromatography TLC (dichloromethane: methanol (v / v) = 20: 1) to obtain the standard product HY-B031 (2.6 mg) as a white solid. |
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