Structure of 4-(Hydroxymethyl)benzoic acid
CAS No.: 3006-96-0
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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. : | 3006-96-0 |
| Formula : | C8H8O3 |
| M.W : | 152.15 |
| SMILES Code : | C1=CC(=CC=C1C(O)=O)CO |
| MDL No. : | MFCD00017598 |
| InChI Key : | WWYFPDXEIFBNKE-UHFFFAOYSA-N |
| Pubchem ID : | 76360 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
| Num. heavy atoms | 11 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.12 |
| Num. rotatable bonds | 2 |
| Num. H-bond acceptors | 3.0 |
| Num. H-bond donors | 2.0 |
| Molar Refractivity | 39.53 |
| TPSA ? Topological Polar Surface Area: Calculated from |
57.53 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.27 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.93 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.73 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.05 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.06 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.01 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-1.64 |
| Solubility | 3.48 mg/ml ; 0.0229 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-1.72 |
| Solubility | 2.87 mg/ml ; 0.0189 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.58 |
| Solubility | 3.97 mg/ml ; 0.0261 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 |
-6.57 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 |
0.56 |
| 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) |
1.0 |
* 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 |
|---|---|---|
| 21% | With Sn-Beta molecular sieve; In 1,4-dioxane; at 190℃; under 52476.2 Torr; for 12h;High pressure; Autoclave; | A series of experiments were conducted to test the variables related to the conversion of 5-hydroxymethyl-2-furoic acid (HMFA) to 4-hydroxymethylbenzoic acid (HMBA). This transformation is a key intermediate step in the transformation of hydroxymethyl furfural (HMF) to (purified) terephthalic acid (PTA), according to: The results are shown in Tables 8 and FIG. 9. Reaction conditions for FIG. 9 were 1000 psig ethylene at 190° C., 10 g of a 100 mM dioxane solution of HFMA, with 100 mg Sn-Beta catalyst. [TABLE-US-00008] TABLE 8 All reactions were run at 850-1000 psig total pressure, 190° C., 10 g of a 100 mM HFMA solution, 100 mg catalyst. HMFA HMBA HMBA Entry Catalyst Solvent Time (hr) Converson (percent) Yield (percent) Selectivity (percent) 1 Sn-Beta dioxane 0.5 18 4 22 2 Sn-Beta dioxane 2 36 11 31 3 Sn-Beta dioxane 4 57 15 26 4 Sn-Beta dioxane 6 61 19 31 5 Sn-Beta dioxane 12 76 21 28 dioxane/water 6 Sn-Beta 1:1 v/v 0.5 94 0 0 7 Sn-Beta THF+ 0.5 35 2 6 8 Zr-Beta dioxane 6 87 9 10 9 None dioxane 2 5 0 0 10 None dioxane 6 21 0 0 11 Si-Beta dioxane 2 20 0 0 12 Si-Beta dioxane 6 56 13 Si-MFI dioxane 2 25 0 0 |
| 19% | In 1,4-dioxane; at 20 - 190℃; under 27752.8 - 52505.3 Torr; for 6h;Inert atmosphere; | General procedure: Experiments were carried out in a 50-mL high pressure stainless steel batch reactor (Parr Series 4590) equipped with a magnetic stirrer and heater. The reactor setup allowed for ethylene gas(Matheson, 99.995percent purity) or helium to be charged to the reactor. In a typical experiment, 100 mg of catalyst and 10 g of a 0.1 M diene solution in dioxane (Sigma-Aldrich, 99.8percent) was loaded into the reactor. The magnetic stirrer was operated at 200 rpm and the head space of the reactor was purged with helium gas with a fill/vent cycle (10×). Next, the reactor was pressurized to 37 bar (room temperature) with ethylene gas, the inlet valve was closed, and the reaction was performed in batch operation. The reactor was heated to 190 °C within 15 min while the pressure increased autogenously to 70 bar. At the end of the reaction time, the reactor was allowed to cool to room temperature and the reactor gases were vented. The product was then collected for analysis. |

[ 3006-96-0 ]
[ 71989-23-6 ]
[ 145069-56-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| AM-PS (0.1 mmol, 118 mg, loading 0.85 mmol g-1) was swelled in DMF for 10 min. To a solution of Rink amide linker (217 mg, 0.4 mmol) and Cl-HOBt (68 mg,0.4 mmol) in DMF (3 mL) was added DIC (62 mul, 0.4 mmol) and the solution was added to the drained resin. The mixture was allowed to stand for 90 min, drained, and washed with DMF. The Kaiser test was negative. The Fmoc group was removed with 20% piperidine (25 min), washed with DMF, and a solution of HMBA (46 mg, 0.3 mmol), Cl-HOBt (101 mg,0.6 mmol), and DIC (63 muL, 0.4 mmol) was added. The reaction was left to proceed overnight, at which point a negative Kaiser test was obtained. Fmoc-Ile-OH (106 mg, 0.3 mmol) was dissolved in DMF (3 mL), DIC (63 muL, 0.4 mmol) was added, and the resultant solution was added to the resin. A solution of DMAP (122 muL, 10 mgmL-1, 0.01 mmol) was added and the mixture shaken for 1 h. The resin was drained and washed with DMF and the procedure repeated twice more to ensure complete esterification. Any remaining hydroxyl groups were capped with 20% (v/v) acetic anhydride in DMF with a catalytic amount of DMAP (0.01 mmol) for 30 min. A total of 203 mg of resin was collected, on which the peptide was elongated as described to afford resin-bound linear peptide. Cyclisation and resin cleavage afforded lassomycin-HMBA-NH2 (125 mg, 62% yield, 64% purity; m/z (ESI-MS) 500.7, (M+4H)4+ requires 500.8). Crude lassomycin-HMBA-NH2 (15 mg, 7.65 mmol) was dissolved in methanol (7.65 mL), cooled to 0 C, and NaOMe (165 mg, 3.06 mmol) was added to give a final concentrationof 0.4 M. The solution was stored at 0 C for 1 h, quenched with TFA (0.58 mL) to give a final TFA concentration of 1M, concentrated under a stream of nitrogen, dissolved in 50% aq.CH3CN containing 0.1 %TFA, and lyophilised. In parallel, a second portion (14 mg) was also subjected to the above conditions. Pooling of both batches and purification by HPLC afforded lassomycin-OMe 1 (4.12 mg, 20% yield). m/z (ESI-MS) 470.9, (M+4H)4+ requires 471.0; 627.5, (M+3H)3+ requires 627.7. Deconvolution yields a mass of 1879.60.07 Da. The calculated mass is 1880.2 Da. |

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