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Structure of 4-(Chloromethyl)benzoic acid
CAS No.: 1642-81-5
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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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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 1642-81-5 |
Formula : | C8H7ClO2 |
M.W : | 170.59 |
SMILES Code : | O=C(O)C1=CC=C(CCl)C=C1 |
MDL No. : | MFCD00002568 |
InChI Key : | OITNBJHJJGMFBN-UHFFFAOYSA-N |
Pubchem ID : | 74234 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P301+P330+P331-P303+P361+P353-P363-P304+P340-P310-P321-P260-P264-P280-P305+P351+P338-P405-P501 |
Class: | 8 |
UN#: | 1759 |
Packing Group: | Ⅱ |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.16 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.49 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.12 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.97 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.18 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.0 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.5 |
Solubility | 0.533 mg/ml ; 0.00313 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.53 |
Solubility | 0.498 mg/ml ; 0.00292 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.79 |
Solubility | 0.279 mg/ml ; 0.00164 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 |
-5.84 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 |
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) |
1.15 |
* 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 |
---|---|---|
Dimethylformamide (2 ml), thionyl chloride (290.4 ml), 1,4-dioxane (1000 ml) and 4- (chloromethyl)benzoic acid (200 g) were placed in a reaction flask, and the mixture was heated for 10 to 12 hours at 65-70C. The resulting mass was distilled under vacuum at below 50C to produce an oily mass. N-(5-Amino-2-methylphenyl)-4-(3-pyridinyl)-2- pyrimidineamine (294 g) was taken in another reaction flask, tetrahydroiuran (800 ml) was added, and the mixture was cooled to -6C. The oily mass and pyridine (640 ml) at -5C to 5C were added to the resulting mixture simultaneously over a period of 1 hour to 1 hour 30 minutes. Tetrahydroiuran was added to the resulting mass portion wise (400 ml + 200 ml + 400 ml + 400 ml + 400 ml + 200 ml) followed by stirring for 1 hour at -5C to 5C. The reaction mass was quenched into water (9.2 L) and potassium carbonate (294 g) at 20-30C, the flask was washed with water (1600 ml) and the reaction mass was stirred for 2 hours at 20-30C. The resulting solid was filtered and washed with water (1600 ml). The wet material was added to acetone (3732.8 ml) and stirred for 1 hour at 20-30C. The separated solid was filtered, washed with acetone (800 ml) and then dried in air over at 55-65C to produce 424 g of 4-chloromethyl-N-[4-methyl-3-[[4-(3-pyridinyl)-2- pyrimidinyl] amino ]phenyl]benzamide (Purity by HPLC: 95.95%).Content of Impurities measured by HPLC:1. 4-Methylbenzamide impurity at 2.94 RRT: 1.8%. | ||
With triethylamine; In N,N-dimethyl-formamide; for 2h; | The 5 mmol of 6 - methyl - N - (4 - (pyridine -3 - yl) pyrimidine -2 - yl) benzene - 1, 3 - diamine 1 (purchased from Shanghai white yuan chemical) and 7 mmol triethylamine in 15 ml N, N - dimethyl formamide in cooling to zero degree Celsius. In a stirring state, addition of 5.5 mmol of 4 - (chloromethyl) benzoyl chloride (purchased from Alfa - Aesar) and the zero degree Celcius stirring for 2 hours. The reaction system is extracted with ethyl acetate, the combined organic phase and drying with anhydrous sodium sulfate. The rotary evaporator to remove the solvent, the crude product by silica gel chromatographic column to separate the product 4 - (chloromethyl) - N - (4 - methyl -3 - ((4 - (pyridine -3 - yl) pyrimidine -2 - yl) amino) phenyl) benzamide |
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