Structure of 51068-78-1
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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. : | 51068-78-1 |
Formula : | C6H11NO3 |
M.W : | 145.16 |
SMILES Code : | O=C(N1CCOCC1)CO |
MDL No. : | MFCD08436413 |
InChI Key : | PHCSTEJVICOGEJ-UHFFFAOYSA-N |
Pubchem ID : | 6480484 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.83 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 38.1 |
TPSA ? Topological Polar Surface Area: Calculated from |
49.77 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.33 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-1.87 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.54 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.26 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.05 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.66 |
Log S (ESOL):? ESOL: Topological method implemented from |
0.57 |
Solubility | 539.0 mg/ml ; 3.72 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (Ali)? Ali: Topological method implemented from |
1.34 |
Solubility | 3210.0 mg/ml ; 22.1 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
0.18 |
Solubility | 219.0 mg/ml ; 1.51 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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 |
-8.51 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 |
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) |
1.47 |
* 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 |
---|---|---|
at 150℃; for 3h; | EXAMPLE 172; 4-[7-(2-Morpholin-4-yl-2-oxo-ethoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid (4-pyrrolidin-1-yl-phenyl)-amide; a. 4-[7-(2-Morpholin-4-yl-2-oxo-ethoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester; A mixture of morpholine (107.4 mg, 1.23 mmol) and methyl glycolate (77.5 mg, 860 mumol) was stirred at 150° C. for 3 hr. The resulting homogeneous clear amber oil was taken up in toluene (2.x.2 mL) with repeated rotary evaporation to remove methanol. The residue was taken up in dry THF (860 muL) and KOtBu was added (113 mg, 1.01 mmol). The mixture was stirred at 100° C. for 5-10 min until a brown slurry formed with no visible chunks. The mixture was then allowed to cool to rt, 4-(7-fluoro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester (302 mg, 912 mumol), as prepared in Example 65b, was added, and the resulting nearly homogeneous reddish-brown solution was stirred at rt for 1 hr, at which point the reaction solidified into a paste. The reaction was taken up in DCM (4 mL) and washed with 1M NaHCO3 (1.x.2 mL) and 1M NaH2PO4 (1.x.2 mL), and the organic layer was dried (Na2SO4) and concentrated. The residue was purified by silica flash chromatography (9:1 DCM/acetone-->8:2-->8:2 DCM/acetone/3percent DMEA eluent) to provide the title compound as a pale yellow oil (94.8 mg, 24percent over two steps). LC/MS (ESI): calcd mass 456.2, found 457.3 (MH)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 172; 4-[7-(2-Morpholin-4-yl-2-oxo-ethoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid (4-pyrrolidin-1-yl-phenyl)-amide; a. 4-[7-(2-Morpholin-4-yl-2-oxo-ethoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester; A mixture of morpholine (107.4 mg, 1.23 mmol) and methyl glycolate (77.5 mg, 860 mumol) was stirred at 150° C. for 3 hr. The resulting homogeneous clear amber oil was taken up in toluene (2.x.2 mL) with repeated rotary evaporation to remove methanol. The residue was taken up in dry THF (860 muL) and KOtBu was added (113 mg, 1.01 mmol). The mixture was stirred at 100° C. for 5-10 min until a brown slurry formed with no visible chunks. The mixture was then allowed to cool to rt, 4-(7-fluoro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester (302 mg, 912 mumol), as prepared in Example 65b, was added, and the resulting nearly homogeneous reddish-brown solution was stirred at rt for 1 hr, at which point the reaction solidified into a paste. The reaction was taken up in DCM (4 mL) and washed with 1M NaHCO3 (1.x.2 mL) and 1M NaH2PO4 (1.x.2 mL), and the organic layer was dried (Na2SO4) and concentrated. The residue was purified by silica flash chromatography (9:1 DCM/acetone-->8:2-->8:2 DCM/acetone/3percent DMEA eluent) to provide the title compound as a pale yellow oil (94.8 mg, 24percent over two steps). LC/MS (ESI): calcd mass 456.2, found 457.3 (MH)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen;Cu/Al2O3/SiO2; In methanol; at 170℃; under 41254.1 Torr; for 16.5h;Autoclave; | HydrogenationThe hydrogenation experiments were performed in a multi-autoclave unit containing four 60 ml batch autoclaves, all equipped with common electrical heating and with individual gas entrainment impellers, manometers and temperature indication . The hydrogenation catalysts were activated in-situ (typical conditions : 230 0C, 10 - 20 bar H2 for 4 hrs ) . The substrates, dissolved in ca . 20 ml solvent , were introduced into the autoclaves by injection. Then, the autoclaves were pressurized with Hz, stirred at 800 rpm and heated to ca. 170 0C. After the reaction, the liquid reactor contents were analyzed by GC-MS. Table 2 shows the reaction conditions and analytical results from the different experiments. Table 23 This specie was qualitatively observed by NMR analysis and/or GC-MS.4 GC-MS peak area percentage (Anpercent) = (peak area n) x 100 / (sum of substrate, 2-hydroxyacetamide, MEG, HOCH2CH2NR2, R2NCH2CH2NR2 and all polyamine peak areas) .5 MEG peak corrected for overlaying methyl glycolate peak (10percent peak area reduction) . n.d. = not determined |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 288h; | Example Id, Preparation of Compound of Formula (Id) A. Preparation of a Compound of Formula (1) in which n is l Rl is 2-{morpholin- 4-yl)-2-oxoethoxy, m is 0, R5 is hydrogen, and R3 is methyl To a solution of (S)-tert~bu.tyl ( 1 -(5-fluoro-4-oxo-3 -phenyl-3 ,4~dihydroquiiiazolra~2~ yt)echyl}carbamate (500 mg, 1 JO mmol) in DMF (2 mL) was added 2-hydroxy-l~ (morpholin-4-yi)ethan-l-one (283 mg, 1.95 mmol) and freshly ground K2CO3 (198 mg, 1.43 mmol). The mixture was heated to 80°C and allowed to stir for 12 days. The reaction was adsorbed directly onto isolute and purified on 1SCG (40 g silica, 0 - 100percent EtOAc/hexane) to give (S)-tert-butyl il-(5-(2~mc>^holmo-2-oxoetiii0xy)^ 2-yl)ethyl)carbamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With lithium hexamethyldisilazane; In tetrahydrofuran; at 23℃; for 5h; | Compound 1-11A solution of 2-hydroxy-l-morpholinoethanone (18 mg, 3 equiv.) in THF was treated with LiHMDS (0.120 mL, 3 equiv.) at 23 °C, followed closely with Inter mediate-2 (15 mg, 1 equiv.). The mixture was stirred at 23 °C for 5 h, then partitioned between a 1 : 1 mixture of ethyl acetate and saturated aqueous ammonium chloride solution. The layers were separated, and the aqueous layer was extracted with ethyl acetate (x3). The organic portions were combined and washed with brine. The mixture was dried over MgS04, filtered, and concentrated in vacuo. The crude material was purified via silica gel chromatography utilizing a 0-80percent ethyl acetate/hexanes gradient to deliver the desired compound (14.7 mg, 75percent) as a white solid. 1H-NMR (500 MHz, CDCls) delta 8.47 (d, 1 H), 8.45 (d, 1 H), 7.30 (s, 1 H), 7.23-7.18 (m, 1 H), 7.03 (ddd, 1 H), 6.98 (td, 1 H), 6.85 (td, 1 H), 6.57 (d, 1 H), 5.96 (s, 2 H), 5.21 (s, 2 H), 3.78-3.63 (m, 4 H), 3.63-3.55 (m, 4 H). |
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