Cat.NO.:A155605,A1477072,A155605,A1477072 Purity:97%,98%,97%,98%
Product Details of [ 1003845-08-6 ]
CAS No. : | 1003845-08-6 |
Formula : |
C10H14BClN2O2 |
M.W : |
240.49
|
SMILES Code : | CC1(C)OB(OC1(C)C)C1=CN=C(Cl)N=C1 |
MDL No. : | MFCD11856048 |
InChI Key : | VLAPDEKXZLRRKV-UHFFFAOYSA-N |
Pubchem ID : | 51341943 |
Safety of [ 1003845-08-6 ]
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Computational Chemistry of [ 1003845-08-6 ] Show Less
Physicochemical Properties
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.6 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 63.52 |
TPSA ?
Topological Polar Surface Area: Calculated from |
44.24 Ų |
Lipophilicity
Log Po/w (iLOGP)?
iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)?
XLOGP3: Atomistic and knowledge-based method calculated by |
2.15 |
Log Po/w (WLOGP)?
WLOGP: Atomistic method implemented from |
1.43 |
Log Po/w (MLOGP)?
MLOGP: Topological method implemented from |
0.41 |
Log Po/w (SILICOS-IT)?
SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.42 |
Consensus Log Po/w?
Consensus Log Po/w: Average of all five predictions |
1.08 |
Water Solubility
Log S (ESOL):?
ESOL: Topological method implemented from |
-2.9 |
Solubility | 0.305 mg/ml ; 0.00127 mol/l |
Class?
Solubility class: Log S scale |
Soluble |
Log S (Ali)?
Ali: Topological method implemented from |
-2.71 |
Solubility | 0.468 mg/ml ; 0.00194 mol/l |
Class?
Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)?
SILICOS-IT: Fragmental method calculated by |
-3.87 |
Solubility | 0.0321 mg/ml ; 0.000134 mol/l |
Class?
Solubility class: Log S scale |
Soluble |
Pharmacokinetics
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) |
Yes |
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) |
Yes |
Log Kp (skin permeation)?
Skin permeation: QSPR model implemented from |
-6.24 cm/s |
Druglikeness
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 |
Medicinal Chemistry
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) |
2.87 |
Application In Synthesis of [ 1003845-08-6 ]
* 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.
- Upstream synthesis route of [ 1003845-08-6 ]
- Downstream synthetic route of [ 1003845-08-6 ]
[ 1003845-08-6 ] Synthesis Path-Upstream 1~3
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With magnesium sulfate In toluene at 20℃; for 15 h; | 34). Synthesis of 2-chloro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidine; To a solution of 5-bromo-2-chloro-pyrimidine (10 mmol, 1.93 g) and triisopropyl borate (12 mmol, 2.8 ml.) in toluene (16 ml) and THF (4 mi_) is added n-buty. lithium \r, hexane (1.58 M, 12 mmol, 7.6 mL) dropwise at -78 0C over 45 min and stirred at -78 0C for 1 hour. The mixture is warmed to -20 0C, then added aq. hydrogen chloride (1M, 20 mL). The mixture is warmed to room temperature. The precipitate is collected and washed with hexane to give a colorless powder (808 mg, 51percent). A mixture of the powder (3.63 mmol, 575 mg), pinacol (3.81 mmol, 450 mg) and MgSO4 (18.15 mmol, 2.2 g) in toluene (10 mL) is <n=”192″/>stirred at room temperature for 15 hour. The mixture is filtrated and the solution is concentrated under reduced pressure. The resultant solid is washed with water to give 2- chloro-5-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-pyrimidine (875 mg, quant); ESI-MS m/z: 159 [M+1-pinacol]\ Retention time 1.75 min (condition A). |
100% | With magnesium sulfate In toluene at 20℃; for 15 h; | Example 14; 1) Synthesis of 2-chloro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidine To a solution of 5-bromo-2-chloro-pyrimidine (10 mmol, 1.93 g) and triisopropyl borate (12 mmol, 2.8 mL) in toluene (16 mL) and THF (4 mL) is added n-butyl lithium in hexane (1.58 M, 12 mmol, 7.6 mL) dropwise at -78° C. over 45 min and stirred at -78° C. for 1 hour. The mixture is warmed to -20° C., then added aqueous 1 M HCl (20 mL). The mixture is warmed to room temperature. The precipitate is collected and washed with hexane to give a colorless powder (808 mg, 51percent). A mixture of the powder (3.63 mmol, 575 mg), pinacol (3.81 mmol, 450 mg) and MgSO4 (18.15 mmol, 2.2 g) in toluene (10 mL) is stirred at room temperature for 15 hour. The mixture is filtrated and the solution is concentrated under reduced pressure. The resultant solid is washed with water to give 2-chloro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidine (875 mg, quant); ESI-MS m/z: 159 [M+1-pinacol]+, Retention time 1.75 min (condition A). |
[1] Patent: WO2008/9435, 2008, A1, . Location in patent: Page/Page column 189-190.
[2] Patent: US2009/118287, 2009, A1, . Location in patent: Page/Page column 67-68.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1 h; Stage #2: at -78 – 20℃; for 5 h; |
Synthesis of Intermediate 1-1 (0337) 1.93 g (10 mmol) of 5-bromo-2-chloropyrimidine was dissolved in 200 mL of THF, and then, at a temperature of −78° C., 4 mL (2.5M in hexane) of normal butyllithium was added thereto. At the same temperature about one hour thereafter, 2.0 mL (10 mmol) of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane was added thereto. At room temperature, the result was stirred for about 5 hours, and then, water was added thereto and a washing process was performed three times thereon using diethylether (100 mL). A washed diethylether layer was dried by using MgSO4, and then, dried under reduced pressure, thereby obtaining a product. The product was separation-purified by silica gel column chromatography, thus preparing 1.56 g (Yield 65percent) of Intermediate 1-1. |
[1] Patent: US2017/179408, 2017, A1, . Location in patent: Paragraph 0336-0337.
[2] Patent: CN104788482, 2016, B, . Location in patent: Paragraph 0023.
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