Structure of Amphos
CAS No.: 932710-63-9
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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. : | 932710-63-9 |
Formula : | C16H28NP |
M.W : | 265.37 |
SMILES Code : | CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1 |
MDL No. : | MFCD09265102 |
InChI Key : | IQTHEAQKKVAXGV-UHFFFAOYSA-N |
Pubchem ID : | 11714598 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.62 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 87.85 |
TPSA ? Topological Polar Surface Area: Calculated from |
16.83 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.57 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.58 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.46 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.37 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.39 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.72 |
Solubility | 0.0502 mg/ml ; 0.000189 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.62 |
Solubility | 0.0637 mg/ml ; 0.00024 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.04 |
Solubility | 0.00241 mg/ml ; 0.0000091 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
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 |
-5.38 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
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 |
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) |
3.47 |
* 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 |
---|---|---|
96% | With dmap; copper (I) acetate In toluene at 120℃; for 8 h; Inert atmosphere | Under argon protection,To the drying reactor was added 1 L of toluene,Followed by the addition of N, N-dimethylaniline (121 g, 1 mol)4-dimethylaminopyridine (122 g, 1 mol),Cuprous acetate (1.2 g, 0.01 mmol)And di-tert-butylphosphonium chloride (181 g, 1 mol)And then heated to 120 C for 8 hours.After completion of the reaction, 1 L of water was added to the quenching reaction,Then extracted,The organic layer was dried over anhydrous magnesium sulfate,filter,After distillation under reduced pressure to give a yellow solid,This was lyophilized in 1 L of n-hexane to recrystallize to give a white solid [4- (N, N-dimethylamino) phenyl] di-tert-butylphosphine 254 g,Yield 96percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: at -30℃; for 0.166667 h; Inert atmosphere Stage #2: With ammonium chloride In water at -30℃; for 0.5 h; |
The reaction system is cooled to -30 ° C, under the protection of nitrogen flow,Adding catalyst to remove water by vacuum dryingAfter the powder was 10.2 g, the reaction was stirred for 10 min.Further, 930 g of di-tert-butylphosphonium chloride was added dropwise.The dropping process controls the reaction temperature below -30 ° C, and the dropwise addition is completed, and the temperature is raised to 50 ° C for 3 hours to obtain di-tert-butyl-4-dimethylaminophenylphosphine. The reaction system was again cooled to -30 ° C, and 1.5 L of a saturated aqueous solution of ammonium chloride was added dropwise with stirring.After stirring for 0.5 h, the mixture was allowed to stand for stratification under the protection of a nitrogen stream.The liquid is separated, and the upper organic phase is concentrated and concentrated to obtain a yellow viscous material for high vacuum distillation under reduced pressure.The degree of vacuum is 0.3-0.5 mmHg, and the fraction of 120 ° C - 140 ° C is collected, and after cooling, it is an off-white solid.That is, the ligand di-tert-butyl-4-dimethylaminophenylphosphine has a yield of 1145-1160 g, a purity of not less than 97percent, and a yield of 81.5percent to 85.0percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: at -60℃; for 0.133333 h; Inert atmosphere Stage #2: With ammonium chloride In water at -60℃; for 0.5 h; |
The reaction system is cooled to -60 ° C under the protection of nitrogen flow.Adding catalyst to the vacuum drying to remove water, copper bromideAfter the powder was 14.8 g, the reaction was stirred for 8 min, and 930 g of di-tert-butylphosphonium chloride was added dropwise.The dropping process controls the reaction temperature below -60 ° C, and the dropwise addition is completed, and the temperature is raised to 55 ° C for 4 hours to obtain di-tert-butyl-4-dimethylaminophenylphosphine. The reaction system was again cooled to below -60 ° C, and 1.5 L of a saturated aqueous solution of ammonium chloride was added dropwise with stirring, and the mixture was stirred for 0.5 h.After standing and layering,The liquid is separated under the protection of a nitrogen stream, and the upper organic phase is concentrated and concentrated to obtain a yellow viscous material for high vacuum distillation under reduced pressure.The degree of vacuum is 0.3-0.5 mmHg, and the fraction of 120 ° C - 140 ° C is collected, and after cooling, it is an off-white solid.It is a ligand of di-tert-butyl-4-dimethylaminophenylphosphine, and the yield is 1145-1160 g, the purity is not less than 97percent, and the yield is 81.5percent to 85.0percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49.2 g | Stage #1: With n-butyllithium In hexane; toluene at 50℃; for 12 h; Inert atmosphere Stage #2: at 5℃; for 12 h; Inert atmosphere |
The reaction flask was replaced with a nitrogen atmosphere, and 32 g of di-tert-butylphosphine and 200 mL of toluene were added to 1 L of the reaction flask,Start the magnetic stirrer, add 0.1M 2.5M n-butyllithium at -10 ° C, drip to 50 ° C for 12 hours, drop the temperature of the reaction solution to -10 ° C,A solution of 40 g of N, N-dimethyl-p-bromoaniline in toluene was added dropwise to the reaction at 50 ° C for 12 hours, after which the reaction solution was lowered to room temperature,10 mL of triethylamine aqueous solution was added dropwise under ice-cooling, and the upper organic phase was depiltrated under nitrogen protection,Distillation under reduced pressure, collecting 120 ° C (15 mm Hg) di-tert-butyl-4-dimethylaminophenylphosphine 49.2 g |
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