Structure of 30727-14-1
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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. : | 30727-14-1 |
Formula : | C6H13NO |
M.W : | 115.17 |
SMILES Code : | OC1CN(CC)CC1 |
MDL No. : | MFCD00003179 |
InChI Key : | IDBNECMSCRAUNU-UHFFFAOYSA-N |
Pubchem ID : | 98203 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H227-H315-H319 |
Precautionary Statements: | P210-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 36.81 |
TPSA ? Topological Polar Surface Area: Calculated from |
23.47 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.64 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.14 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.31 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.21 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.51 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.44 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.58 |
Solubility | 30.6 mg/ml ; 0.265 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.19 |
Solubility | 74.5 mg/ml ; 0.647 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.26 |
Solubility | 63.9 mg/ml ; 0.555 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 |
-6.9 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) |
1.53 |
* 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 |
---|---|---|
The title compound was prepared by using Mitsunobu condition from 4-(2-hydroxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester and 1-Ethyl-3-pyrrolidinol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride; In N,N-dimethyl-formamide; | 1 g (0.0042 mol) of 2-Cyclohexyl-2-fur-2-yl-2-hydroxyacetic acid methyl ester was dissolved in 12 ml of EtOH and 6 ml of a solution of NaOH 2N were added. This mixture was stirred at 60 for 1 hour. After this time, the EtOH was evaporated and the residue was acidified with HCI 10%. The aqueous solution was extracted with AcOEt (2 x 100 ml). the organic layers were combined, dried and evaporated to obtain a residue (2- cyclohexyl-2-fur-2-yl-2-hydroxyacetic acid) which was used without further purification. The acid obtained was dissolved in dry DMF (12 ml) and 0.817 g (0.005 mol) of 1,1'- carbonildimidazol were added. The mixture was stirred for 1 h at room temperature. After this time the sodium salt of 1-ethylpyrrolidin-3-ol (prepared by addition of HNa (0. 11g, 0.0046 mol) to a solution of 1-ethylpyrrolidin-3-ol (0. 531g, 0.0046 mol) in 5 ml of dry DMF) was added. After stirring 15 h at room temperature the reaction mixture was treated with water, and the aqueous phase was extracted with Et2O (2 x 100 ml). The organic phases were combined, washed with water and dried. After removal of the solvent the product obtained was purified by chromatography on silica gel eluting with chloroform plus isopropanol (5% 15%). The yield was 460 mg (34% related to starting methyl ester) of the title product. 'H-NMR (CDCI3) : 6 1.05-1. 45 (m, 10H), 1.60-2. 10 (m, 4H), 2.10-2. 35 (m, 2H), 2.40-2. 75 (m, 5H), 2.85-3. 0 (m, 1 H), 3.76 (bs, OH, 1 H), 5.27 (m, 1 H), 6.30-6. 40 (m, 2H), 7.39 (s, 1 H). MS [M+1]' : 322 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | In N,N-dimethyl-formamide; | EXAMPLE 170 Preparation of 4-[(1-Ethylpyrrolidin-3-yl)oxy]phenyl 2-[4-[2-(1-Pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl Ketone. STR515 Sodium hydride (60% oil dispersion, 38 mg) was suspended in DMF (1 mL) and stirred at ambient temperature for 15 min under argon before <strong>[30727-14-1]1-ethyl-3-pyrrolidinol</strong> (92 muL) was added. After stirring for 15 min, 4-fluorophenyl 2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl ketone (223 mg) in 1 mL of DMF was introduced and the resulting solution was stirred at ambient temperature for 4 h. The reaction mixture was diluted with brine (50 mL) and extracted with EtOAc (3*50 mL). The combined organic layers were dried (Na2 SO4) and concentrated under reduced pressure. Chromatography with Et3 N:MeOH:EtOAc (5:5:90) afforded the product as a colorless oil (171 mg, 63%). 1 H NMR (CDCl3): delta 7.85 (m, 1H), 7.75 (d, 2H), 7.65 (m, 1H), 7.35 (d, 2H), 7.32 (m, 2H), 6.78 (d, 2H), 6.71 (d, 2H), 4.80 (m, 1H), 4.03 (t, 2H), 2.85 (t, 2H), 2.80 (m, 2H), 2.60 (m, 4H), 2.50 (m, 4H), 2.28 (m, 1H), 1.92 (m, 1H), 1.08 (t, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium hydroxide; In dichloromethane; | EXAMPLE 51 Trans-4-(2-ethoxypnenoxy)-1-ethyl-3-pyrrolidinol A mixture of 17.0 g. (0.15 mole) of 1-ethyl-3,4-epoxypyrrolidine, 22.1 g. (0.16 mole) of o-ethoxyphenol and 3 drops of concentrted hydrochloric acid was heated on a steam bath overnight. The oil was dissolved in methylene chloride and washed with three 50-ml. portions of 5% sodium hydroxide and one 50-ml. portion of water. The methylene chloride solution was dried over anhydrous sodium sulfate, concentrated and chromatographed on silica gel to give 8.1 g. (21%) of an oil which crystallized on standing. The solid was recrystallized from cyclohexane to yield a tan solid, m.p. 73-75 C. Analysis: Calculated for C14 H21 NO3: C,66.90; H,8.42; N,5.57; Found: C,66.49; H,8.43; N,5.48. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Under a dry nitrogen atmosphere, a stirred mixture of 0.24 mL (0.002 mole) of l-ethyl-3-pyrrolidinol in 5 mL of ethylene glycol dimethyl ether was cooled to0C and 1.38 mL of methyllithium (1.6 molar solution in diethyl ether, 0.0022 mole) was added. Upon completion of addition, the resultant mixture was stirred for ten minutes.A second reaction vessel was flushed with dry nitrogen and 0.2 gram of copper(I) chloride (0.002 mole) was added to it. The reaction mixture prepared EPO <DP n="31"/>above was then added to the copper(I) chloride and the mixture was stirred at ambient temperature for about 30 minutes. While maintaining a dry nitrogen atmosphere, 0.94 gram (0.0022 mole) of 5-((4-iodophenyl)methoxy)-l,2- dichloronaphthalene and 20 mL of pyridine were then added. Upon completion of addition, the reaction mixture was heated to reflux where it stirred for 48 hours. The mixture was then cooled and concentrated under reduced pressure to a residue. The residue was slurried in a mixture of ethyl acetate and water and the mixture was filtered through a pad of silicon dioxide filter agent. An organic phase was separated and was washed first with an aqueous copper(II) sulfate solution, then with a saturated aqueous sodium chloride solution. The organic phase was dried with anhydrous magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to a residue. The residue was purified by column chromatography on silica gel, eluted with mixtures of 6% to 10% methanol in methylene chloride. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.13 gram of the title compound. The NMR spectrum was consistent with the proposed structure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | 0.655 g (0.00297 mol) of (2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetic acid were dissolved in 8 ml of dry DMF. To this solution 0.580 g (0.0036 mol) of 1, 1'- carbonildiimidazol were added and the mixture was stirred at room temperature for 1 h. After this time, the mixture obtained was added to a suspension (cooled at 0C) of 1- ethylpyrrolidin-3-ol (0.390 ml g, 0.0033 mol) and HNa (0.078 g, 0.0033 mol) in 4 ml of dry DMF. After stirring 15 h at room temperature the reaction mixture was treated with water and extracted three times with Et2O. The organic layers were combined, washed with water and dried. The residue was purified by silica gel column chromatography (eluent : CHCI3 plus isopropanol 0%No.5%) to obtain 610 mg (65%) of the title product as an oil. 'H-NMR (CDCI3) :. 61. 05-1.15 (m, 3H), 1.25-1. 95 (m, 10H), 2.10-2. 35 (m, 1H), 2.40- 3.0 (m, 6H), 3.79 (bs, 1 H, OH), 5.23 (m, 1 H), 7.24-7. 36 (m, 3H), 7.65-7. 67 (m, 2H). MS [M+ir : 318 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃;Inert atmosphere; | [00490] l-Ethyl-3-(3-methyl-4-nitro-phenoxy)-pyrrolidine (35a): To a magnetically stirred solution of 3-methyl-4-nitrophenol 34a (0.8 g, 5.09 mmol) in anhydrous THF (17 mL) was added DIAD (1.51 mL, 7.64 mmol), PPh3 (2 g, 7.64 mmol) and l-ethylpyrrolidin-3-ol (645 mg, 5.6 mmol) at room temperature and was allowed to stir overnight under nitrogen atmosphere. Upon completion, the solvent was evaporated under vacuum and the residue purified by silica gel flash chromatography (0- 100% MeOH/DCM) to yield l-ethyl-3-(3-methyl-4-nitrophenoxy) pyrrolidine 35a for which the structure was established based on proton NMR and mass spectroscopy. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | A 25 mL round bottom flask was charged with compound 39 Oxalyl chloride (240 mL, 2.5 mmol) and methylene chloride (10 mL) were then added to the flask, was stirred at room temperature for 24 hours and triethylamine (625 mul, 4.5 mmol) and 4-morpholinopropylamine (151 mg, 1.05 mmol) was added to the flask, and the mixture was stirred at room temperature for 8 hours.The residue was diluted with dichloromethane (100 mL), washed successively with 1M hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography (dichloromethane / methanol = 50/1) to give Compound 48 (628 mg, 94 %). Compound 39 was reacted with <strong>[30727-14-1]1-ethyl-3-hydroxy-tetrahydropyrrole</strong> (138 mg, 1.2 mmol) to give compound 56 (305 mg, 48%), as in the preparation of compound 48. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66.1% | In water; at 10 - 120℃; under 6750.68 Torr; for 10h;Autoclave; Sealed tube; | General procedure: This embodiment is 3-hydroxy-1-methyl tetrahydropyrrole preparation method, the specific steps are as follows: A 500 mL four-necked flask was charged with 250 g of a 40 wt% aqueous solution of monomethylamine and cooled to 10 C in an ice-water bath. Then, while stirring, 102 g of 1,4-dichloro-2-butanol was added dropwise and the temperature was controlled at 15 C The following, about 15min drip finished; Then pour the system into 500mLAutoclave, sealed, evacuated to a pressure of 1.0 ± 0.1MPa, while heated to 120 ± 2 , the reaction was stirred for about 10h, GC control of raw materials disappear. After the reaction was over, cooled to room temperature, the material was discharged, batchwise add 110g of sodium hydroxide, release a large amount of methylamine gas, control the temperature below 50 , precipitated a lot of white solid, stirred for 1h; filtration, the filtrate layered, the upper organic phase Ethanol 100mLAnd anhydrous magnesium sulfate 18g, stirring 2 ~ 3h; and then filtered, the filtrate was concentrated in vacuo to give a yellow transparent oily liquid, and then vacuum distillation to give 46.7g of colorless and transparent 3-hydroxy-1-methyl tetrahydropyrrole , Yield 64.8%, purity 99.3% (HPLC). |
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