Structure of 3236-48-4
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 3236-48-4 |
Formula : | C8H16O2 |
M.W : | 144.21 |
SMILES Code : | OC[C@H]1CC[C@H](CO)CC1 |
MDL No. : | MFCD00066360 |
InChI Key : | YIMQCDZDWXUDCA-UHFFFAOYSA-N |
Pubchem ID : | 7735 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 10 |
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 | 40.78 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.88 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.57 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.78 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.9 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.21 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.96 |
Solubility | 15.8 mg/ml ; 0.109 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.99 |
Solubility | 14.7 mg/ml ; 0.102 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.72 |
Solubility | 27.4 mg/ml ; 0.19 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 |
-6.77 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) |
2.28 |
* 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 triethylamine; In dichloromethane; at -20 - 20℃; for 10h; | Step 2: 4-Toluenesulfonyl chloride (742.5 g, 3.75 mol) was added to a solution of trans-cyclohexane-1,4-diyldimethanol (500 g, 4.17 mol) and Et3N (695 g, 5 mol) in DCM (6000 mL) at -20° C. The mixture was stirred at room temperature for 10 h and then quenched with water (10 L). The organic layer was separated, the aqueous layer was extracted with DCM (2*3 L), and the combined organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to give trans-4-(hydroxymethyl)cyclohexylmethyl 4-methylbenzenesulfonate as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With 1H-imidazole; In DMF (N,N-dimethyl-formamide); at 25℃; for 16h; | To a 100 mL-flask containing 79 (4.0 g, 27.8 mmol) in DMF (40 mL) was added TBDMSCl (3.56 g, 23.6 mmol) and imidazole (3.79 g, 55.6 mmol). The reaction was allowed to stir at 25 C. for 16 hours after which time saturated aqueous LiBr (50 mL) was added and the reaction extracted with ether (2×50 mL). The ether layers were pooled and extracted again with LiBr (2×35 mL). The ether layer became clear. The ether layer was then concentrated in vacuo and the product purified by flash chromatography, on a silica gel column, eluting with 1:2 ether/petroleum ether to yield 83 (3.80 g, 62%) as a homogenous oil. 1H NMR (CDCl3) delta 3.46 (d, J=6.2 Hz, 2H), 3.39 (d, J=6.2 Hz, 2H), 1.95-1.72 (m, 4H), 1.65 (m, 1H), 1.40 (m, 1H), 1.03-0.89 (m, 4H), 0.88 (s, 9H), 0.04 (s, 6H); 13C NMR (CDCl3) delta 69.2, 69.1, 41.2, 41.1, 29.5, 26.5, 18.9, -4.8; APCI m/z (rel intensity) 259 (MH+, 100). |
45.1% | With 1H-imidazole; In N,N-dimethyl-formamide; at 0 - 25℃; for 16h; | To a 500-mL flask containing(lR,4R)-cyclohexane-l,4-diyldimethanol (80 g, 555 mmol) and 1H- imidazole (37.8 g, 555 mmol) in DMF (400 mL) was added to a solution of tert- butylchlorodimethylsilane (84 g, 555 mmol) in DMF (400 mL) at about 0C. After addition, the reaction was allowed to stir at about 25C for about 16 h. The solution was poured into ice water (200 mL) and extracted with MTBE (3x100 mL). The organics were combined, concentrated in vacuo, and purified by flash chromatography on silica gel (1 :2 EtOAc/petroleum ether) to afford the title compound (68 g, 45.1 %); lH NMR (400MHz, CDC13) delta 0.03 (s, 6 H) 0.86 - 0.96 (m, 13 H) 1.34 - 1.58 (m, 3 H) 1.81 (d, J=8.61 Hz, 4 H) 3.42 (dd, J=17.61, 6.26 Hz, 4 H) |
With 1H-imidazole; In N,N-dimethyl-formamide; | To a solution of trans-<strong>[3236-48-4]1,4-cyclohexanedimethanol</strong> (3.46 g, 24.0 mmol) in DMF (40 ml) was added ten?butyldimethylsilyl chloride (3.01 g, 20 mmol) and imidazole (3.27 g, 48.0 mmol). The reaction was allowed to stir overnight. The reaction was then partitioned between ether and brine. The organic layer was separated, washed with brine, dried over sodium sulfate,filtered and evaporated. The crude product was purified on a Biotage 40M silica gel column, eluting with a gradient of 10-50% ethyl acetate in hexanes to give the title compound. NMRo (ppm)(CDCl3): 3.46 (d, 2H), 3.40 (d, 2H), 1.81 (m, 4H), 1.42 (m, 2H), 1.26 (s, 1H), 0.94 (m, 4H), 0.89 (s, 9H), 0.03 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28.6% | Thionyl chloride (16.6g, 139.5mmol) was added dropwise to a stirred solution of trans-cyclohexane-1,4-dicarboxylic acid (10.0g, 58.1mmol) in methanol (160mL) at 0?20°C. The resulting mixture was stirred at reflux for 4h. The resulting solution was evaporated in vacuo and the residue was partitioned between aqueous water (50mL) and dichloromethane (100mL). The organic layer was washed with aqueous NaHCO3 (40mL), brine (50mL) and dried (Na2SO4), and evaporated in vacuo to give a colorless solid (9.8g, 84.0percent). Next, a mixture of this solid (9.8g) and NaBH4 (18.5g, 488.2mmol) in THF (196mL) was stirred at reflux for 0.5h. Then methanol (69mL) was added to the resulting solution at room temperature. The resulting solution was stirred at reflux for 12h and quenched with 30percent hydrochloric acid (20mL) in and ice bath. The resulting mixture was stirred for 1h and alkalized with 50percent sodium hydroxide solution (30mL). The resultant mixture was extracted with dichloromethane (3×60mL). The combined organic extracts were dried (MgSO4) and evaporated in vacuo to give 42 (2.4g, 28.6percent) as a colorless solid. Mp: 63?65°C. 1H NMR (CDCl3): delta 0.93?1.03 (m, 4H), 1.45?1.47 (m, 2H), 1.84?1.88 (m, 4H), 3.40?3.46 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.6% | With Ni/NiO-diatomite; at 200℃; for 3h;Autoclave; Inert atmosphere; | 200 m of 1,4-cyclohexane dimethanol (trans isomer 67percent, cis isomer 33percent) and 200 m of the catalyst shown in the following Table 1 were introduced into a 500 ml autoclave(Comparative Example 6 is no catalyst) And the mixture was stirred at 200°C For 3 hours in a nitrogen atmosphere. |
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