Structure of 17739-45-6
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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. : | 17739-45-6 |
Formula : | C7H13BrO2 |
M.W : | 209.08 |
SMILES Code : | BrCCOC1CCCCO1 |
MDL No. : | MFCD01321310 |
InChI Key : | GCUOLJOTJRUDIZ-UHFFFAOYSA-N |
Pubchem ID : | 86621 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 43.69 |
TPSA ? Topological Polar Surface Area: Calculated from |
18.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.51 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.7 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.92 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.47 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.22 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.97 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.01 |
Solubility | 2.05 mg/ml ; 0.00979 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.7 |
Solubility | 4.14 mg/ml ; 0.0198 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.19 |
Solubility | 1.36 mg/ml ; 0.0065 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 |
-6.37 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 |
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) |
3.45 |
* 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 potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 20 - 60℃; for 22h; | A mixture of the phenol from example 22 (1.29 g, 2.65 mmol), potassium carbonate (690 mg, 5 mmol), and 2-(2-bromoethoxy)tetrahydro-2H-pyran (840 mg, 4 mmol) in 1-methyl-2-pyrrolidinone (10 ml), was heated at 60 C. for 4 hours, followed by a further 18 hours at room temperature. The mixture was diluted with ethyl acetate and washed with water (*3), then brine, dried (MgSO4) and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using ethyl acetate as the eluant to afford the title compound as a white foam, 1.20 g. 1H-NMR (CDCl3, 400 MHz) delta: 1.37 (m, 2H), 1.46 (m, 2H), 1.61 (m, 4H), 1.76 (m, 4H), 1.92 (m, 4H), 2.33 (s, 3H), 2.43 (m, 2H), 2.72 (m, 4H), 3.39 (m, 1H), 3.72 (m, 1H), 3.86 (m, 1H), 4.13 (m, 3H), 4.30 (t, 2H), 4.54 (m, 1H), 5.24 (m, 1H), 6.87 (d, 1H), 7.21 (d, 1H), 8.04 (m, 3H), 8.13 (d, 1H), 8.26 (dd, 1H). LRMS: m/z APCI- 614 [M-H-] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 80℃; for 18h; | A mixture of <strong>[78208-72-7]ethyl 5-isopropyl-1H-pyrazole-3-carboxylate</strong> (Chem. and Pharm. Bull. 1984; 32(4);1568) (509 mg, 2.8 mmol), 2-(2-bromoethoxy)tetrahydro-2-pyran (732 mg, 3.5 mmol) and potassium carbonate (483 mg, 3.5 mmol) in 1-methyl-2-pyrrolidinone (5 ml) was stirred at 80° C. for 18 hours. The cooled mixture was poured into ethyl acetate and washed with water and brine, then dried (MgSO4) and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (20:80 to 40:60) to afford the title compound of preparation 34 as a clear oil, 663 mg. [0469] 1HNMR (CDCl3, 400 MHz) delta: 1.25 (d, 6H), 1.37 (t, 3H), 1.44-1.71 (m, 6H), 2.97 (m, 1H), 3.42 (m, 1H), 3.54 (m, 1H), 3.75 (m, 1H), 4.00 (m, 1H), 4.32 (q, 2H), 4.54 (t, 1H), 4.68 (m, 1H), 4.76 (m, 1H), 6.64 (s, 1H). [0470] LRMS: m/z ACPI+ 311 [MH]+ [0471] Further elution provided the title compound of preparation 35, 242 mg. [0472] 1HNMR (CDCl3, 400 MHz) delta: 1.25 (d, 6H), 1.38 (t, 3H), 1.46-1.72 (m, 6H), 3.15 (m, 1H), 3.45 (m, 1H), 3.65 (m, 1H), 3.81 (m, 1H), 4.10 (m, 1H), 4.34 (m, 2H), 4.39 (m, 2H), 4.49 (t, 1H), 6.57 (s, 1H). [0473] LRMS: m/z ACPI+ 311 [MH]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; lithium iodide; In 1-methyl-pyrrolidin-2-one; at 80℃; for 24h; | Preparation 18 2-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazole-3-carboxylic acid ETHVL ester Ethyl-pyrazole-3-carboxylate (980mg, 7. 0MMOL), 2- (2-bromoethoxy)-tetrahydro- 2H-pyran (1.57g, 7. 5MMOL), potassium carbonate (1. 01G, 7. 3MMOL) and lithium iodide (46. 8mg, 0. 35MMOL) were dissolved in 1-METHYL-2-PYRROLIDINONE (1 OML) and the reaction mixture heated to 80°C for 24 hours. The reaction mixture was allowed to cool for 17 hours and then diluted with a mixture of ethyl acetate: water 1: 1 (500mL). The organic layer was washed with water (3X250ML), dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with cyclohexane : ethyl acetate 90: 10 to 80 : 20 to 75: 25 to 50: 50. The appropriate fractions were combined and concentrated in vacuo to yield the title product. HNMR (CDCI3, 400MHZ) : 1.40 (t, 3H), 1.42-1. 80 (m, 6H), 3.43 (m, 1H), 3.60 (m, 1H), 3. 78 (m, 1H), 4.04 (m, 1H), 4.35 (q, 2H), 4.55 (m, 1H), 4.82 (m, 2H), 6.81 (m, 1 H), 7. 48 (m, 1 H). MS ES+ m/z 291 [MNa] + |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 80℃; for 18h; | Preparation 14 5-ISOPROPYL-1-R2- (TETRAHVDRO-PVRAN-2-YLOXV)-ETHYLL-1 H-PYRAZOLE-3-CARBOXYLID ethyl ester The ester of preparation 6 (509mg, 2. 8MMOL), 2- (2-bromoethoxy) tetrahydro-2H- pyran (732mg, 3. 5MMOL) and potassium carbonate (483mg, 3. 5MMOL) were dissolved in 1-methyl-2-pyrrolidinone (5mL) and the reaction mixture heated to 80°C for 18 hours. The reaction mixture was cooled, poured into ethyl acetate, washed with water (x 2) and brine, dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with pentane: ethyl acetate 80: 20 to 60: 40 to yield the title product, 663mg (76percent). HNMR (CD3, 400MHZ) : 1.25 (d, 6H), 1.37 (t, 3H), 1.44-1. 71 (m, 6H), 2.97 (m, 1 H), 3.42 (m, 1 H), 3.54 (m, 1 H), 3.75 (m, 1 H), 4.00 (m, 1 H), 4.32 (m, 2H), 4.54 (t, 1 H), 4.68 (m, 1 H), 4.76 (m, 1 H), 6.64 (s, 1 H). MS ES+ M/Z 227 [MH] + |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(2) The following reagent and solvent were put into a reaction container. sodium hydride: 1.4 g N,N-dimethylformamide: 200 ml After the reaction solution was cooled to 0 C., the compound obtained in the item (1) was added gradually. Subsequently, the reaction solution was agitated for 2 hours while the temperature of the reaction solution was raised to room temperature. Then, 6.4 ml of 2-(2-bromoethoxy)tetrahydro-2H-pyran was added, the reaction solution was heated to 60 C., and agitation was performed at this temperature (60 C.) for 5 hours. At this time, the degree of proceeding of the reaction was ascertained with TLC appropriately. Thereafter, the reaction was terminated with an ammonium chloride aqueous solution, and an organic phase was extracted with ethyl acetate. The resulting organic phase was washed with water and saturated saline solution in that order and was dried with anhydrous magnesium sulfate. A crude product obtained by concentrating the organic phase under reduced pressure was refined through column chromatography. The thus obtained product was used as-is in the following step |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | (S)-2-((Tert-butoxycarbonyl)amino)-2-(4-hydroxyphenyl)acetic acid (2.67 g, 10.0 mmol) was dissolved in 70 mL of dimethylformamide and the solution was cooled in an ice bath. Sodium hydride (0.88 g, 60% in mineral oil, 22.0 mmol) was added in portions. The mixture was stirred for thirty minutes before 2-(2-bromoethoxy)tetrahydro-2H-pyran (2.30 g, 1 1.0 mmol) in 30 mL of dimethylformamide was added portionally. The reaction mixture was stirred at room temperature for 17 hours. Sodium hydride (0.16 g) was added and reaction was continued for one hour and then diluted with ice/water. The mixture was extracted with ethyl acetate (100 mL chi 2). The aqueous layer was cooled in an ice bath and acidified using 1.5 M aqueous potassium hydrogen sulfate to pH 2-3. The resulting mixture was extracted with ethyl acetate (100 mL chi 2). The organic phase was washed with water, brine, and dried over sodium sulfate. The product (3.3 g) was obtained (yield: 84%). NMR (500 MHz, CDCI3): delta 7.32 (m, 2H), 6.92 (m, 2H), 5.55 (m, 0.5H), 5.28 (m, 0.5H), 4.74 (m, I H), 4.15 (m, 2H), 4.05 (m, IH), 3.90 (m, I H), 3.85 (m, I H), 3.55 (m, I H), 1 .85 (m, I H), 1.75 (m, I H), 1.60 (m, 5H), 1.45 (s, 5H), 1.28 (s, 4H); MS (EI) for C20H29NO7; 394 (MH"). | |
84% | Step 1 : Preparation of (2S)-2-((tert-butoxycarbonyl)amino)-2-(4-(2- ((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)phenyl)acetic acid. [00125] <strong>[69651-48-5](S)-2-((tert-butoxycarbonyl)amino)-2-(4-hydroxyphenyl)acetic acid</strong> (2.67 g, 10.0 mmol) was dissolved in 70 mL of dimethylformamide and the solution was cooled in an ice bath. Sodium hydride (0.88 g, 60% in mineral oil, 22.0 mmol) was added in portions. The mixture was stirred for thirty minutes before 2-(2-bromoethoxy)tetrahydro-2H-pyran (2.30 g, 1 1.0 mmol) in 30 mL of dimethylformamide was added portionally. The reaction mixture was stirred at room temperature for 17 hours and then diluted with ice/water. The mixture was extracted with ethyl acetate (50 mL chi 2). The aqueous layer was cooled in an ice bath and acidified using 1.5 M aqueous potassium hydrogen sulfate to pH 2-3. The resulting mixture was extracted with ethyl acetate (100 mL chi 2). The organic phase was washed with water, brine, and then dried over sodium sulfate. The product (3.3 g) was obtained after removing the solvent and drying under high vacuum (yield: 84%). XH NMR (500 MHz, CDC13): delta 7.32 (m, 2H), 6.92 (m, 2H), 5.55 (m, 0.5H), 5.28 (m, 0.5H), 4.74 (m, 1H), 4.15 (m, 2H), 4.05 (m, 1H), 3.90 (m, 1H), 3.85 (m, 1H), 3.55 (m, 1H), 1.85 (m, 1H), 1.75 (m, 1H), 1.60 (m, 5H), 1.45 (s, 5H), 1.28 (s, 4H); MS (EI) for C20H29NO7; 394 (MH"). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 80℃; for 16h; | To a solution of methyl3-nitro-1H-pyrazole-5-carboxylate (1.7 g, 10.0 mmol) in Nl'Vl:P(20 mL) was added 2-(2-bromoethoxy)tetrahydro-2H-pyran (2.6 g, 13.0 mmol), followed byK2C03 (1. 7 g, 13.0 mmol). The resulting mixture was stirred at 80 C for 16 hrs. Then K~C03was filtered off. The filtrate was concentrated in vacuo to give a residue, which was purified bysilica gel column (PE;EA = 2/l) to afford methyl3-nitro-l-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-pyrazole-5-carboxylate (2.8 g, yield: 94%) as yellow oil.[00948] 1H NMR (400 lVlliz, CDCh): (5 = 7.39 (s, 1H), 4.92 (t, J = 7.2 Hz, 2H), 4.57 (s, 1H),4.11-4.07 (m, lH), 3.98 (overlap, lH), 3.96 (s, 3H), 3.84-3.80 (m, lH), 3.64-3.60 (m, IH), 3.49-3.46 (m, lH), 1.67-1.46 (m, 6H). |
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