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Structure of 10465-81-3
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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. : | 10465-81-3 |
Formula : | C12H20N4O2 |
M.W : | 252.31 |
SMILES Code : | O=C(/N=N/C(N1CCCCC1)=O)N2CCCCC2 |
MDL No. : | MFCD00010111 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H315-H319-H228 |
Precautionary Statements: | P240-P210-P241-P264-P280-P302+P352-P370+P378-P337+P313-P305+P351+P338-P362+P364-P332+P313 |
Class: | 4.1 |
UN#: | 1325 |
Packing Group: | Ⅱ |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.83 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 75.23 |
TPSA ? Topological Polar Surface Area: Calculated from |
65.34 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.99 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.86 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.89 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.43 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.47 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.13 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.31 |
Solubility | 1.23 mg/ml ; 0.00487 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.85 |
Solubility | 0.354 mg/ml ; 0.0014 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.33 |
Solubility | 11.9 mg/ml ; 0.047 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) |
Yes |
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 |
-6.52 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 |
1.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.69 |
* 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 |
---|---|---|
With triphenylphosphine; In tetrahydrofuran; hexane; ethyl acetate; | Example 220 Ethyl 5-[2-(5-methyl-2-phenyl-1,3-thiazol-4-yl)ethoxy]-1H-indole-2-carboxylate A solution of ethyl 5(hydroxy)-1H-indole-2-carboxylate (991 mg, 4.83 mmol) and 2-(5-methyl-2-phenyl-1,3-thiazol-4-yl)ethanol (1.06 g, 4.83 mmol) in tetrahydrofuran (30 +5 mL rinse) was added to a stirred mixture of triphenylphosphine (1.3 g, 4.9 mmol) and 1,1'-(azodicarbonyl)dipiperidine (1.2 g, 4.9 mmol) in tetrahydrofuran (10 mL). The reaction was stirred for 48 h and then diluted with ethyl acetate (200 mL). This solution was washed successively with water, 10% hydrochloric acid, and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. Flash chromatography of the residue over silica gel using 25% ethyl acetate/hexane gave 1.04 g (53%) of the desired product. The product had: 1H NMR (300 MHz, acetone-D6) 10.40-10.55 (br s, 1 H), 7.89-7.95 (m, 2 H), 7.38-7.49 (m, 4 H), 7.19 (d, 1 H), 7.06-7.09 (m, 1 H), 6.95 (dd, 1 H), 4.30-4.40 (m, 4 H), 3.20 (t, 2 H), 2.51 (s, 3 H), 1.35 (t, 3 H); mass spectrometry gave MH+=407.1 (calc'd exact mass for C23H22N2O3S=406.14). The following compounds were prepared according to the method of Example 220: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | In tetrahydrofuran; dichloromethane; | A. 2-(4-Fluorophenyl)-1-[4-(1-methylpyrrolidin-3-yloxy)benzyl]-6-(phenylmethoxy)-1,2,3,4-tetrahydroisoquinoline To a solution of 2-(4-fluorophenyl)-1-(4-hydroxybenzyl)-6-(phenylmethoxy)-1,2,3,4-tetrahydroisoquinoline (0.450 g, 1.02 mmol) in THF (5 ml) was added <strong>[13220-33-2]1-methyl-3-pyrrolidinol</strong> (0.22 ml, 2.04 mmol), tri-n-butyl-phosphine (0.5 ml, 2.04 mmol) and 1,1' azodicarbonyl dipiperidine (0.5 g, 2.04 mmol) respectively. Dichloromethane (4 ml) was added and the reaction was allowed to stir overnight. The reaction was diluted with aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried with MgSO4, filtered and concentrated. The product was purified by radial chromatography (100percent CH2Cl2, then CH2Cl2/MeOH, 95:5) to yield the title compound (0.30 g, 56percent yield): ES-MS (m/z) 523 [M+H]+. |
56% | In tetrahydrofuran; dichloromethane; | A. 2-(4-Fluorophenyl)-1-[4-(1-methylpyrrolidin-3-yloxy)benzyl]-6-(phenylmethoxy)-1,2,3,4-tetrahydroisoquinoline To a solution of 2-(4-fluorophenyl)-1-(4-hydroxybenzyl)-6-(phenylmethoxy)-1,2,3,4-tetrahydroisoquinoline (0.450 g, 1.02 mmol) in THF (5 ml) was added <strong>[13220-33-2]1-methyl-3-pyrrolidinol</strong> (0.22 ml, 2.04 mmol), tri-n-butyl-phosphine (0.5 ml, 2.04 mmol) and 1,1'azodicarbonyl dipiperidine (0.5 g, 2.04 mmol) respectively. Dichloromethane (4 ml) was added and the reaction was allowed to stir overnight. The reaction was diluted with aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried with MgSO4, filtered and concentrated. The product was purified by radial chromatography (100percent CH2Cl2, then CH2Cl2/MeOH, 95:5) to yield the title compound (0.30 g, 56percent yield): ES-MS (m/z) 523 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With tributylphosphine; In dichloromethane; acetone; | Alternatively the racemate may be made as follows: 1,1'-(Azodicarbonyl)dipiperidine (560 mg, 2.2 mmol) was added in portions to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (240 mg, 0.75 mmol), (prepared as described for the starting material in Example 2), 1-methyl-3-piperidinemethanol (115 mg, 0.89 mmol) and tributylphosphine (440 mg, 2.2 mmol) in methylene chloride (10 ml). The mixture was stirred for 18 hours, diluted with ether and the resulting precipitate was removed by filtration. The volatiles were removed from the filtrate by evaporation, and the residue was dissolved in acetone and ethereal hydrogen chloride (1.5 ml of a 1M solution, 1.5 mmol) was added. The precipitated product was collected by filtration and purified by column chromatography eluding with methylene chloride/methanol/aqueous ammonia (75/8/1). The purified solid product was triturated with ether collected by filtration and dried to give 4-(4chloro-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-3-ylmethoxy)quinazoline (105 mg, 33percent). m.p. 211-212° C.; 1H NMR Spectrum: (DMSOd6) 1.08(m, 1H); 1.50(m, 1H); 1.78(m, 4H); 2.08(m, 1H); 2.16(m, 3H); 2.62(m, 1H); 2.82(m, 1H); 3.95(s, 3H); 4.00(d, 2H); 7.18(s, 1H); 7.32(m, 1H); 7.52(dd, 1H); 7.58(t, 1H); 7.79(s, 1H); 8.35(s, 1H); 9.52(s, 1H); MS-ESI: 431 [MH]+; Elemental analysis: Found C, 59.9; H, 5.5; N, 12.9; C22H24N4O2ClF 0.5H2O Requires C, 60.0; H, 5.7; N, 12.7percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tributylphosphine; In benzene; | Step 4 To an ice-cooled mixture of 2(R)-(4-methoxybenzenesulfonylamino)-3-methylbutyric acid benzyl ester (5 g, 13.25 mmol) [prepared as described in Example 2 above], N-tert-butoxycarbonyl-5-indole methanol (3.8 g, 14.6 mmol) and tributylphosphine (3.6 mL, 14.6 mmol) in dry benzene (60 mL) was added [1,1'-azodicarbonyl]dipiperidine (3.68 g, 14.6 mmol). The reaction mixture was stirred overnight at room temperature and then chromatographed on a silica gel column eluding with (5-10%) ethyl acetate/hexanes to give of 2(R)-[(N-tert-butoxy-carbonylindol-5-ylmethyl)-(4-methoxybenzenesulfonyl)amino]-3-methylbutyric acid benzyl ester (6.5 g) as a white foamy semi-solid. |
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