Structure of 73368-41-9
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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. : | 73368-41-9 |
Formula : | C10H13NO3 |
M.W : | 195.22 |
SMILES Code : | CCOC(=O)C1=CC=C(N)C(OC)=C1 |
MDL No. : | MFCD14543019 |
Boiling Point : | No data available |
InChI Key : | DZXKUQHCFAKAJP-UHFFFAOYSA-N |
Pubchem ID : | 11788808 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.3 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 53.42 |
TPSA ? Topological Polar Surface Area: Calculated from |
61.55 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.2 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.45 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.46 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.36 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.35 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.57 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.02 |
Solubility | 1.88 mg/ml ; 0.00962 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.35 |
Solubility | 0.875 mg/ml ; 0.00448 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.65 |
Solubility | 0.436 mg/ml ; 0.00223 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 |
-6.46 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 |
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) |
1.78 |
* 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 |
---|---|---|
87% | With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; XPhos; In tert-butyl alcohol; at 100℃; for 20.0h; | (R)-ethyl 4-((8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2- yl)amino)-3-methoxybenzoate (i?)-2-chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one (88.4 mg, 0.30 mmol, 1 eq), ethyl 4-amino-3-methoxybenzoate (70.3 mg, 0.36 mmol, 1.2 eq), Pd2dba3 (13.7 mg, 0.015 mmol, 5 mol%), XPhos (21.5 mg, 0.045 mmol, 15 mol%) and K2C03 (166 mg, 1.2 mmol, 4 eq) were dissolved in tBuOH (3 mL, 0.1 M) and heated to 100 C for 20 hours. The mixture was filtered through celite, washed with DCM and condensed. Purification by column chromatography (ISCO, 4 g silica column, 0-100% EtOAc/hexanes, 12 minute gradient) gave the desired product as a dark yellow oil (119 mg, 0.262 mmol, 87%). 1H NMR (400 MHz, Chloroform-;/) delta 8.57 (d, J= 8.5 Hz, 1H), 7.68 (tt, J = 4.2, 2.1 Hz, 3H), 7.53 (d, J= 1.4 Hz, 1H), 4.50 (q, J= 7.4 Hz, 1H), 4.36 (qd, J= 7.1, 1.2 Hz, 2H), 4.22 (dd, J= 7.8, 3.6 Hz, 1H), 3.96 (d, J= 1.2 Hz, 3H), 3.32 (d, J= 1.3 Hz, 3H), 2.22 - 2.10 (m, 1H), 2.04 - 1.96 (m, 1H), 1.89 - 1.78 (m, 4H), 1.70 (dq, J= 14.2, 8.2, 7.4 Hz, 4H), 1.39 (td, J= 7.1, 1.2 Hz, 3H), 0.91 - 0.82 (m, 3H). LCMS 453.80 (M+H). |
77% | With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; XPhos; In tert-butyl alcohol; at 100℃; for 21.0h; | <strong>[755039-55-5](R)-2-chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one</strong> (44.2 mg, 0.15 mmol, 1 eq), ethyl 4-amino-3-methoxybenzoate (35.1 mg, 0.18 mmol, 1.2 eq), Pd2dba3 (6.9 mg, 0.0075 mmol, 5 mol %), XPhos (10.7 mg, 0.0225 mmol, 15 mol %) and potassium carbonate (82.9 mg, 0.60 mmol, 4 eq) were dissolved in tBuOH (1.5 mL, 0.1 M) and heated to 100 C. After 21 hours, the mixture was cooled to room temperature, filtered through celite, washed with DCM and concentrated under reduced pressure. Purification by column chromatography (ISCO, 4 g silica column, 0-100% EtOAc/hexanes over an 18 minute gradient) gave a yellow oil (52.3 mg, 0.1 15 mmol, 77%). NMR (400 MHz, Chloroform- delta 8.57 (d, J = 8.5 Hz, 1H), 7.69 (td, J = 6.2, 2.9 Hz, 2H), 7.54 (d, J = 1.8 Hz, 1H), 4.52 (t, J = 7.9 Hz, 1H), 4.37 (q, J = 7.1 Hz, 2H), 4.23 (dd, J = 7.9, 3.7 Hz, 1H), 3.97 (s, 3H), 3.33 (s, 3H), 2.20 - 2.12 (m, 1H), 2.03 - 1.97 (m, 1H), 1.86 (ddd, J = 13.9, 7.6, 3.6 Hz, 4H), 1.78 - 1.65 (m, 4H), 1.40 (t, J = 7.1 Hz, 3H), 0.88 (t, J = 7.5 Hz, 3H). LCMS 454.32 (M+H). |
77% | With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; XPhos; In tert-butyl alcohol; at 100℃; for 21.0h; | <strong>[755039-55-5](R)-2-chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one</strong> (44.2 mg, 0.15 mmol, 1 eq), ethyl 4-amino-3-methoxybenzoate (35.1 mg, 0.18 mmol, 1.2 eq), Pd2dba3 (6.9 mg, 0.0075 mmol, 5 mol %), XPhos (10.7 mg, 0.0225 mmol, 15 mol %) and potassium carbonate (82.9 mg, 0.60 mmol, 4 eq) were dissolved in tBuOH (1.5 mL, 0.1 M) and heated to 100 C. After 21 hours, the mixture was cooled to room temperature, filtered through celite, washed with DCM and concentrated under reduced pressure. Purification by column chromatography (ISCO, 4 g silica column, 0-100% EtOAc/hexanes over an 18 minute gradient) gave a yellow oil (52.3 mg, 0.115 mmol, 77%). 1H NMR (400 MHz, Chloroform-d) delta 8.57 (d, J=8.5 Hz, 1H), 7.69 (td, J=6.2, 2.9 Hz, 2H), 7.54 (d, J=1.8 Hz, 1H), 4.52 (t, J=7.9 Hz, 1H), 4.37 (q, J=7.1 Hz, 2H), 4.23 (dd, J=7.9, 3.7 Hz, 1H), 3.97 (s, 3H), 3.33 (s, 3H), 2.20-2.12 (m, 1H), 2.03-1.97 (m, 1H), 1.86 (ddd, J=13.9, 7.6, 3.6 Hz, 4H), 1.78-1.65 (m, 4H), 1.40 (t, J=7.1 Hz, 3H), 0.88 (t, J=7.5 Hz, 3H). LCMS 454.32 (M+H). |
77% | With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; XPhos; In tert-butyl alcohol; at 100℃; for 21.0h; | (R)-2-chloro-8-cyclopentyl-7-ethyl-5 -methyl-7, 8-dihydropteridin-6(51])-one (44.2 mg, 0.15 mmol, 1 eq), ethyl 4-amino-3-methoxybenzoate (35.1 mg, 0.18 mmol, 1.2 eq), Pd2dba3 (6.9mg, 0.0075 mmol, 5 mol %), XPhos (10.7 mg, 0.0225 mmol, 15 mol %) and potassium carbonate(82.9 mg, 0.60 mmol, 4 eq) were dissolved in tBuOH (1.5 mL, 0.1 M) and heated to 100 C. After21 hours, the mixture was cooled to room temperature, filtered through celite, washed with DCMand concentrated under reduced pressure. Purification by column chromatography (ISCO, 4 gsilica column, 0-100% EtOAc/hexanes over an 18 minute gradient) gave a yellow oil (52.3 mg,0.115 mmol, 77%). ?HNMR (400 MHz, Chloroform-cl) 8.57 (d,J= 8.5 Hz, 1H), 7.69 (td,J=6.2, 2.9 Hz, 2H), 7.54 (d, J= 1.8 Hz, 1H), 4.52 (t, J= 7.9 Hz, 1H), 4.37 (q, J= 7.1 Hz, 2H), 4.23(dd, J= 7.9, 3.7 Hz, 1H), 3.97 (s, 3H), 3.33 (s, 3H), 2.20-2.12 (m, 1H), 2.03- 1.97 (m, 1H), 1.86(ddd, J 13.9, 7.6, 3.6 Hz, 4H), 1.78 - 1.65 (m, 4H), 1.40 (t, J 7.1 Hz, 3H), 0.88 (t, J= 7.5 Hz,3H). LCMS 454.32 (M+H). |
77% | With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; XPhos; In tert-butyl alcohol; at 100℃; for 21.0h; | <strong>[755039-55-5](R)-2-chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one</strong> (44.2 mg, 0.15 mmol, 1 eq), ethyl 4-amino-3-methoxybenzoate (35.1 mg, 0.18 mmol, 1.2 eq), Pd2dba3 (6.9 mg, 0.0075 mmol, 5 mol %), XPhos (10.7 mg, 0.0225 mmol, 15 mol %) and potassium carbonate (82.9 mg, 0.60 mmol, 4 eq) were dissolved in tBuOH (1.5 mL, 0.1 M) and heated to 100 C. After 21 hours, the mixture was cooled to room temperature, filtered through celite, washed with DCM and concentrated under reduced pressure. Purification by column chromatography (ISCO, 4 g silica column, 0-100% EtOAc/hexanes over an 18 minute gradient) gave a yellow oil (52.3 mg, 0.115 mmol, 77%). 1H NMR (400 MHz, Chloroform-d) delta 8.57 (d, J = 8.5 Hz, 1H), 7.69 (td, J = 6.2, 2.9 Hz, 2H), 7.54 (d, J = 1.8 Hz, 1H), 4.52 (t, J = 7.9 Hz, 1H), 4.37 (q, J = 7.1Hz, 2H), 4.23 (dd, J = 7.9, 3.7 Hz, 1H), 3.97 (s, 3H), 3.33 (s, 3H), 2.20- 2.12 (m, 1H), 2.03- 1.97 (m, 1H), 1.86 (ddd, J = 13.9, 7.6, 3.6 Hz, 4H), 1.78- 1.65 (m, 4H), 1.40 (t, J = 7.1Hz, 3H), 0.88 (t, J = 7.5 Hz, 3H). LCMS 454.32 (M+H). |
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