Structure of 110013-19-9
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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. : | 110013-19-9 |
Formula : | C5H11NO |
M.W : | 101.15 |
SMILES Code : | OC[C@@H]1CNCC1 |
MDL No. : | MFCD09260722 |
InChI Key : | QOTUIIJRVXKSJU-YFKPBYRVSA-N |
Pubchem ID : | 7446911 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 31.91 |
TPSA ? Topological Polar Surface Area: Calculated from |
32.26 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.36 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.5 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.79 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.16 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.7 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.12 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.09 |
Solubility | 83.0 mg/ml ; 0.82 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.29 |
Solubility | 197.0 mg/ml ; 1.95 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.56 |
Solubility | 27.7 mg/ml ; 0.274 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 |
-7.27 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 |
---|---|---|
> 99% | (5) Cphi-t°rtf-Butyl 3-(hydroxymethyl)pyrrolidine-l-carboxylate (2.96 g, 14.7 mmol) in a round bottom flask was mixed with 4N hydrogen chloride in ethyl acetate (30 ml) at room temperature. The mixture was stirred for 2 hours and concentrated in vacuo. The residue was diluted with ethanol (10 ml) and solid potassium carbonate was added. To the resulting slurry was added small amount of water until bubbles were generated. After 2 hours, filtration was performed to remove solid materials and the filtrate was concentrated to yield GS)-pyrrolidin-3-yl-methanol (1.49 g, 14.7 mmol, >99 %) as an orange oil. | |
With trifluoroacetic acid; In dichloromethane; at 20℃; for 16h; | a) tert-Butyl (3S)-3- (HYDROXYMETHYL) PYRROLIDINE-1-CARBOXYLATE (0.9 g, 4.48 mmol), was dissolved in dichloromethane (10 ml) and trifluoroacetic acid (2 ml) was added. The reaction mixture was stirred for 16 hours at ambient temperature. The reaction mixture was concentrated under reduced pressure and then co-evaporated with toluene. The residue was dissolved in methanol (20 ml) and then macroporous carbonate (3 g) was added and the heterogeneous mixture was stirred for 16 hours at ambient temperature to give a pH 9 mixture. The mixture was filtered and the filtrate was concentrated under reduced pressure to give (3S)-pyrrolidin-3-ylmethanol as an oil which was used without further purification: H-NMR (DMSO D6) : 3.25 (m, 2H), 3.10 (m, 3H), 2.85 (m, 1H), 2.30 (m, 1H), 1.90 (m, 1H), 1.60 (m, 1H) ; MS (+ve ESI) : 101 (M+H) +. | |
1.24 g | With acetyl chloride; In methanol; at 20℃;Inert atmosphere; | Intermediate 84: (S)-Pyrrolidin-3-ylmethanol Acetyl chloride (9mL) was added dropwise at 0C to methanol (4OmL) under an atmosphere of nitrogen. The mixture was stirred for 0.5 hours at 0C then tert-butyl (S)-3 - hydroxymethylpyrrolidine-1-carboxylate (2.5g) was added. The resulting solution was stirred at room temperature overnight then concentrated in vacuo. The residue was dissolved inisopropanol (4OmL) and potassium carbonate (lOg) was added. The mixture was stirred at room temperature overnight then filtered. The filtrate was concentrated in vacuo to give (S)pyrrolidin-3-ylmethanol (1.24g) as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | With potassium phosphate; copper(l) iodide; dimethylethanolamine; at 60℃; for 24h; | [002 12j 1 OA. (S)-( 1 -(2-Fluoro-5 -methoxyphenyl)pyrrolidin-3 -yl)methanol: A mixture of <strong>[1028263-94-6]1-fluoro-2-iodo-4-methoxybenzene</strong> (187 mg, 0.74 1 mmol), (S)-pyrrolidin-3-ylmethanol (150 mg, 1.48 mmol), Cul (14 mg, 0.074 mmol) and K3P04 monohydrate (342 mg, 1.48 mmol) in dimethylethanolamine (0.7 mL, 7 mmol) was heated to 60 C for 24 h. The reaction was quenched with sat. aq. NaHCO3. The aqueous layer was extracted with EtOAc and the organic layer was washed with brine, dried (MgSO4), and concentrated. Purification via silica chromatography gave 1OA (22 mg, 0.098 mmol,13% yield). LC-MS Anal. Calc’d for C12H16FN02: 225.25, found [M+H] 226.3. 1HNMR (400 MHz, CDC13) ö 6.88 (dd, J=13.4, 8.6 Hz, 1H), 6.31 - 6.08 (m, 2H), 3.80 -3.75 (s, 3H), 3.72 - 3.64 (m, 2H), 3.55 - 3.43 (m, 2H), 3.42 - 3.34 (m, 1H), 3.29 - 3.21 (m,1H), 2.57 - 2.44 (m, 1H), 2.15 - 2.06 (m, 1H), 1.77 (dd, J=12.5, 7.7 Hz, 1H), 1.64 (br. s,1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In acetonitrile; at 20 - 30℃;Inert atmosphere; | (S)-pyrrolidine-3-methanol (5A) (2 g, 19.77 mmol) was dissolved in 17 acetonitrile (10 ml), and di43 (tert-butyl) dicarbonate (4.75 g, 21.75 mmol) was added thereto, followed by a reaction at room temperature overnight. The solvent was removed to dryness by rotary evaporation under reduced pressure, to obtain 69 tert-butyl (3S)-3-(hydroxymethyl)pyrrolidine-1-carboxylate (5B) as a colorless viscous liquid (3.97 g, yield 100.00%). LCMS m/z =224.2[M+23]. |
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