Structure of 73522-17-5
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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. : | 73522-17-5 |
Formula : | C4H10O2 |
M.W : | 90.12 |
SMILES Code : | CC[C@H](O)CO |
MDL No. : | MFCD09953764 |
InChI Key : | BMRWNKZVCUKKSR-BYPYZUCNSA-N |
Pubchem ID : | 6993189 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 6 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 23.67 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.16 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.25 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.18 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.19 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.15 |
Solubility | 63.3 mg/ml ; 0.703 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.21 |
Solubility | 55.0 mg/ml ; 0.611 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
0.12 |
Solubility | 119.0 mg/ml ; 1.32 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 |
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 |
-6.98 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 |
2.0 |
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) |
1.24 |
* 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 |
---|---|---|
68% | In palladium-carbon; ethanol; | a. Preparation of (2S)-1,2,-butanediol A solution of (2S)-3-butene-1,2-diol which was purchased from Eastman Kodak, (3 g, 0.034 mmoles) in 40 mL of ethanol was hydrogenated in the presence of 300 mg of 10% Pd/C overnight. The so-formed reaction mixture was filtered through celite. The so-formed filter cake was washed with ethanol and the combined filtrates were evaporated to provide 2.08 g (68% yield) of the title compound. |
68% | In palladium-carbon; ethanol; | EXAMPLE 23 STR51 a. Preparation of (2S)-1,2-butanediol A solution of (2S)-3-butene-1,2-diol which was purchased from Eastman Kodak, (3 g, 0.034mmoles) in 40 mL of ethanol was hydrogenated in the presence of 300 mg of 10% Pd/C overnight. The so-formed reaction mixture was filtered through celite. The so-formed filter cake was washed with ethanol and the combined filtrates were evaporated to provide 2.08 g (68% yield) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With water;[(1-SS)-(Dibenzoyl-DTA)]; at 5 - 20℃; for 2.5h;Product distribution / selectivity; | 72 g of racemic 1, 2-epoxybutane was added with 0.4 mole% of the catalyst prepared in Preparation Example 1 [(1-RR)-(Dibenzoyl-LTA) ] (or Preparation Example 2 [ (1-SS) - (Dibenzoyl-DTA)]) and cooled down to 5C. Then 5.4 g of water was slowly added here and stirred at 20Cfor 2.5 hours. The remaining 1,2- epoxybutane was eliminated under reduced pressure and the remains were added with dichloromethane and water. After separation of the water layer and fractional distillation, (R) -1,2- butanediol (or (S) -1, 2-butanediol) were obtained with 98.5%ee optical purity and 55% of yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; In dichloromethane; at 20℃; for 2h;Cooling with ice; | 3. Dial Protection [0198] Procedure A: [0199] To an ice-cooled solution of <strong>[73522-17-5](S)-1,2-butanediol</strong> (100 mg, 1.1 mmol) in dichloromethane (DCM) (0.3 mL) was charged thionyl chloride (0.1 mL, 1.35 mmol) in DCM (0.2 mL), then the ice bath was removed and reaction was aged at ambient temperature for 2 hours to reach completion by 1H NMR monitoring. The reaction was quenched by water with cold bath to keep temperature <25 C. The organic layer was washed with water twice and was directly used in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With tetrabutyl ammonium fluoride; In tetrahydrofuran; at 0 - 20℃; for 6h; | Compound 21 (1.5 g, 4.5 mmol) was dissolved in 20 mL of dry THF and cooled to 0 C. To this, tetra n-butylammonium fluoride (7.7 mL, 7.7 mmol, 1 M solution THF) was added and stirred for 4-6 h at room temperature. The reaction mixture was quenched with saturated ammonium chloride solution (10 mL) and extracted with ethyl acetate (4 * 20 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting crude was purified through column chromatography to afford compound 22 (0.26 g, 4.3 mmol, 95%) as a colorless oil. (c 1.0, CHCl3). IR [NEAT]: 3410, 2966, 2880, 1401, 1059, 989, 768, 540 cm-1. 1H NMR (300 MHz, CDCl3): delta 3.67-3.58 (m, 2H), 3.46-3.40 (m, 1H), 3.12 (br s, 2H), 1.51-1.40 (m, 2H), 1.00 (t, J = 7.5 Hz, 3H) ppm. 13C NMR, 75 MHz, CDCl3: delta 73.7, 66.5, 26.0, 9.9 ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With camphor-10-sulfonic acid; In dichloromethane;Reflux; | Into a 50 mL round bottom flask, diol 22 (0.2 g, 3.3 mmol), CSA (catalytic amount), anisaldehyde dimethyl acetal (0.91 g, 5.0 mmol) and CH2Cl2 (12 mL) were added and refluxed for 20 h. The reaction mixture was quenched with triethylamine (2 mL). The solvent was removed with a rotary evaporator and the resulting crude acetal was directly utilized for the next reaction without further purification. The crude acetal (0.5 g) was dissolved in 15 mL of dry CH2Cl2 and cooled to -78 C. To this, diisobutyaluminium hydride (2.6 mL, 3.6 mmol, and 1.4 M solution in toluene) was added and stirred for 2 h at -30 C. The reaction mixture was quenched with saturated sodium potassium tartrate solution and stirred for 6 h at room temperature. The reaction mixture was extracted with CH2Cl2 (3 * 10 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting crude was purified by column chromatography to afford compound 13 (0.38 g, 1.8 mmol, 80%) as a colorless oil. (c 1.5, CHCl3). IR [NEAT]: 3426, 2926, 2875, 1612, 1586, 1513, 1247, 1034, 820, 516 cm-1. 1H NMR, (300 MHz, CDCl3): delta 7.30-7.26 (m, 2H), 6.90-6.87 (m, 2H), 4.56 (d, J = 11.2 Hz, 1H), 4.46 (d, J = 11.2 Hz, 1H), 3.80 (s, 3H), 3.80-3.72 (m, 1H), 3.70-3.65 (m, 1H), 3.55-3.39 (m, 1H), 1.97 (br s, 1H), 1.72-1.39 (m, 2H), 0.92 (t, J = 7.5 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3): delta 159.2, 129.3, 128.6, 113.9, 80.7, 71.1, 64.9, 55.2, 23.5, 9.6 ppm. MS(ESI): m/z 233 [M+Na]+. HRMS(ESI) m/z calculated for C12H18O3Na 233.11482, found: 233.11446. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With 1H-imidazole; In dichloromethane; at 0 - 20℃; for 1h; | To a solution of 1,2-butanediol 17 (0.6 g, 6.67 mmol), in CH2Cl2 (15 mL) wereadded imidazole (0.45 g, 6.67 mmol) and tertbutyldimethylsilyl chloride(1.0 g, 6.67 mmol) at 0 C. It was stirred for 1 h at room temperature. After completion,the reaction was quenched with water (10 mL), and extracted with CH2Cl2(2 x 20 mL). The combined organic layers were washed with brine (10 mL), dried overNa2SO4 and concentrated under reduced pressure. The cruderesidue was purified by column chromatography (10:90 ethyl acetate / hexanes)to give the 18 (1.08 g, 80%) as a colourless oil. [alpha]30D= -8.5 (c 0.3, CHCl3). IR (neat): nu 2956, 2857, 2111, 1458, 1734, 1253, 1056, 834, 774 cm-1.1H NMR (500 MHz, CDCl3)delta 3.51-3.67 (m, 2H), 3.40 (dd, J = 9.4, 7.4 Hz, 1H), 2.44 (br.s, 1H),1.31-1.59 (m, 2H), 0.96 (t, J = 7.5 5Hz, 3H), .96 (s, 9H), 0 .08 (s, 6H) ppm. 13C NMR (75MHz, CDCl3) delta 73.2, 66.9,29.6, 25.8, 25.7, 9.9, -5.4, -5.3 ppm. ESI-MS (m/z)242 [M+39]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | To a solution of aldehyde 9 (1.0 g,13.8 mmol) in DMSO, were added nitrosobenzene (0.40 g, 5.55 mmol) and D-proline(1.6 g, 13.8 mmol, 20 mol %) in one portion at 25 C. After 1 h, the reactionmixture was cooled to 0 C and then diluted with CH3OH (5 mL). Tothis solution was added excess NaBH4 (0.6 g, 15.6 mmol) slowly. After30 min, the reaction was quenched with sat. NH4Cl. The organic layerwas separated and the aqueous phase was extracted with EtOAc (3 x 10 mL). Thecombined organic phase was dried over anhydrous Na2SO4,then concentrated in vacuo. The residue was dissolved in MeOH (15 mL) and thentreated with 3% copper sulphate over 12 h. After completion, as monitored by TLC,it was quenched with sat. NH4Cl. The organic layer was separated andthe aqueous phase was extracted with EtOAc (3 x 10 mL). The combined organicphase was dried over anhydrous Na2SO4, concentrated invacuo, and purified by silica gel chromatography(silica gel, mixtures of hexanes/ ethyl acetate 50:50) to afford the desired diol17 (0.6 g, 50%). [alpha]30D= -16.8 (c 0.5, CHCl3). IR (neat): nu 3350, 2961, 2926, 2878, 1219, 772 cm-1. 1H NMR (300 MHz, CDCl3) delta 3.68 (d, J = 2.9 Hz, 2H), 3.62-3.67 (m, 2H), 1.45-1.52 (m, 2H), 0.97 (t, J = 7.5 Hz, 3H) ppm. 13C NMR (150 MHz, CDCl3) delta 73.6, 66.2, 25.8, 9.9, 22.6 ppm.EI-MS (m/z)113 [M+23]. |
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