Structure of Tricyclohexylphosphine
CAS No.: 2622-14-2
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CAS No. : | 2622-14-2 |
Formula : | C18H33P |
M.W : | 280.43 |
SMILES Code : | P(C1CCCCC1)(C2CCCCC2)C3CCCCC3 |
MDL No. : | MFCD00003853 |
InChI Key : | WLPUWLXVBWGYMZ-UHFFFAOYSA-N |
Pubchem ID : | 75806 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P362-P403+P233-P405-P501 |
Num. heavy atoms | 19 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 90.27 |
TPSA ? Topological Polar Surface Area: Calculated from |
13.59 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
4.08 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.37 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
6.47 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.61 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.8 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
5.47 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.76 |
Solubility | 0.00483 mg/ml ; 0.0000172 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.41 |
Solubility | 0.00109 mg/ml ; 0.0000039 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.3 |
Solubility | 0.0142 mg/ml ; 0.0000505 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
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) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-4.2 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 |
1.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
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) |
4.25 |
* 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 |
---|---|---|
In dichloromethane-d2; at 20℃; for 2h;NMR tube;Reactivity; | In a dry box, a Teflon-sealed n.m.r. tube was charged with (2S)-methyl 2-N-acetylaminopenta-2,4-dienoate 57 (10.8 mg, 63.9 mumol), Grubbs' catalyst (50.7 mg, 61.6 mumol) and degassed deuterated DCM (CD2Cl2, 0.8 mL) at room temperature. The n.m.r. tube was shaken gently and reaction progress was monitored by 1H and 31P n.m.r. spectroscopy. Compounds were identified by the following diagnostic resonances: 1H n.m.r. (300 MHz, CD2Cl2): After 15 min: Grubbs' catalyst: delta 8.61 (d, J=7.6 Hz, 2H, ortho-Arom CH), 20.05 (s, 1H, [Ru]CHPh); Ruthenium-dienamide complex 73: delta 7.96 (d, J=11.0 Hz, 1H, [Ru]CHCH), 20.11 (d, J=11.0 Hz, 1H, [Ru]CH); Ruthenium-dienamide chelate 74 (trace): delta 15.20 (d, J=4.2 Hz, 1H, [Ru]CH); Ratio of ruthenium complexes [Ru]CHPh: 73: 74=1.0:1.0:<0.1. After 60 min: Grubbs' catalyst: delta 8.45 (d, J=7.6 Hz, 2H, ortho-Arom CH), 20.04 (s, 1H, [Ru]CHPh); Ruthenium-dienamide complex 73: delta 7.96 (d, J=11.0 Hz, 1H, [Ru]CH=CH), 20.10 (d, J=11.0 Hz, 1H, [Ru]CH); Ruthenium-dienamide chelate 74: delta 6.73 (d, J=3.0 Hz, 1H, [Ru]CHCH), 15.19 (d, J=4.2 Hz, 1H, [Ru]CH); Ratio of ruthenium complexes [Ru]CHPh: 73: 74=3:1:1. After 120 min (no change after 18 h): Ruthenium-dienamide chelate 74: delta 6.71 (d, J=3.0 Hz, 1H, [Ru]CHCH), 15.19 (d, J=4.0 Hz, 1H, [Ru]CH). 31P n.m.r. (300 MHz, CDCl3): delta Ruthenium-dienamide chelate 74: 35.0; Grubbs' catalyst: 37.0; Ruthenium-dienamide complex 73: 38.8; Tricyclohexylphosphine oxide: 46.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium chloride; sodium t-butanolate; In 1,2-dimethoxyethane; | Example 5 3-(ETHOXY-HYDROXY-METHYLENE)-3H-INDENE-1-CARBONITRILE, SODIUM SALT A solution of tricyclohexylphosphine (21.5 mg, 0.0770 mmol) in ethylene glycol dimethyl ether (10 mL) under nitrogen was charged with palladium (II) acetate (11.5 mg, 0.0510 mmol). The reaction was stirred at room temperature until the solution was homogenous (approx. 15 minutes), cooled to 0° C. and charged with sodium tert-butoxide (2.53 g, 25.5 mmol). After 5 minutes a solution of 2-bromo-phenylacetonitrile (1.32 mL, 10.2 mmol) and ethyl-3-ethoxyacrylate (1.47 mL, 10.2 mmol) in ethylene glycol dimethyl ether (10 ml) was added dropwise over 10 minutes. Upon complete addition, the reaction was warmed to room temperature then heated to 85° C. for 1 hour. The reaction was cooled to room temperature then diluted with ethyl acetate (50 mL) and poured into aqueous potassium dihydrogen phosphate (0.25 M, 50 mL), pH=7. The aqueous layer was saturated by addition of sodium chloride as solid and the organic layer separated and washed with aqueous saturated sodium chloride (1*50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo affording 3-(ethoxy-hydroxy-methylene)-3H-indene-1-carbonitrile, sodium salt, as a dark brown oil (1.74 g, 84percent) which solidifies on standing. 1H NMR (400 MHz, CD3CN) delta8.04 (d, 1H, J=6.0), 7.58 (s, 1H), 7.43 (d, 1H, J=6.0), 6.98-6.91 (m, 2H), 4.25 (q, 2H, J=7.2), 1.35 (t, 3H, J=7.2); 13C NMR (100 MHz, CD3CN) delta166.7, 135.5, 132.3, 131.3, 122.8, 120.5, 119.0, 118.4, 117.7, 103.3, 79.2, 58.2, 14.6; IR (ATR, neat) 2176, 1597, 1465, 1257, 1195,1068, 1029, 754 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium chloride; sodium t-butanolate; In 1,2-dimethoxyethane; | Example 7 3-(ETHOXY-HYDROXY-METHYLENE)-5,6-DIMETHOXY-3H-INDENE-1-CARBONITRILE, SODIUM SALT A solution of tricyclohexylphosphine (82.0 mg, 0.293 mmol) in ethylene glycol dimethyl ether (10 mL) under nitrogen was charged with palladium (II) acetate (43.7 mg, 0.195 mmol). The reaction was stirred at room temperature until the solution was homogeneous (approx. 15 minutes) and stirred an additional 5 minutes before cooling to 0° C. and charging with sodium tert-butoxide (996 mg, 9.75 mmol). After 5 minutes a solution of 2-bromo-4,5-dimethoxyphenylacetonitrile (1.00 g, 3.90 mmol) and ethyl-3-ethoxyacrylate (0.564 ml, 3.90 mmol) in ethylene glycol dimethyl ether (5 ml) was added dropwise over 10 minutes. Upon complete addition the reaction mixture was warmed to room temperature and then heated to 85° C. for 16 hours. The reaction was cooled to room temperature then diluted with methyl tert-butyl ether (50 mL) and poured into aqueous potassium dihydrogenphosphate (0.25 M, 100 mL). The aqueous layer was separated and solid sodium chloride was added to the aqueous layer until saturated. The aqueous layer was extracted with ethyl acetate (1*125 mL) and this organic layer was washed with aqueous saturated sodium chloride 12*35 ml), dried over sodium sulfate, filtered and concentrated in vacuo affording 3-(ethoxy-hydroxy-methylene)-5,6-dimethoxy-3H-indene-1-carbonitrile, sodium salt, as a dark brown oil (906 mg, 3.3 mmol, 85 percent) which crystallized on standing. 1H NMR (400 MHz, d4-MeOH) delta7.64 (s, 1H), 7.46 (s, 1H), 6.99 (s, 1H), 4.56 (q, 2H, J=7.1), 3.86 (s, 6H), 1.38 (t, 3H, J=7.05); 13C NMR (100 MHz,d4-MeOH) delta167.8, 145.0, 144.5, 130.2, 129.4, 126.4, 123.3, 112.5, 104.0, 102.6, 100.7, 79.0, 58.4, 55.6, 14.1; IR (ATR, neat) 3499, 2164, 1629, 1482, 1449, 1282, 1207, 1157, 1124, 1076, 845, 769 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium acetate; In 1,4-dioxane; | Step 5. Preparation of N-(2,6-difluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propane-1-sulfonamide (SM-14) The mixture of <strong>[1262198-07-1]3-bromo-2,6-difluoroaniline</strong> and N-(3-bromo-2,6-difluorophenyl) propane-1-sulfonamide (560 mg, 2.69 mmol) was combined with bis(pinacolato)diboron (820 mg, 3.23 mmol), tricyclohexylphosphine (52.8 mg, 0.188 mmol), potassium acetate (396 mg, 4.04 mmol), and Pd2 dba3 (74.0 mg, 0.081 mmol) in 1,4-dioxane (10 mL) to give a yellow suspension. The reaction mixture was heated in a oil bath to 120 C. for 2 hours whereupon LCMS indicated complete conversion. The reaction was allowed to cool to room temperature and partitioned between EtOAc and water. The layers were separated and the aqueous portion was extracted with EtOAc. The combine organic portions were washed with water (2*), brine, dried (Na2SO4), and concentrated to give a dark brown oil as a mixture of boronate esters which was used without further purification: N-(2,6-difluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propane-1-sulfonamide LCMS(m/z) 174.0 (MH+, boronic acid); tR=0.33 minute. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium acetate;tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; | Step 2. Preparation of 2,5-difluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline To a solution of 3-bromo-2,5-difluoroaniline (2.0 g, 9.4 mmol), bis(pinacolato)diboron (2.86 g, 11.25 mmol), tricyclohexylphosphine (0.184 g, 0.656 mmol), and potassium acetate (1.380 g, 14.06 mmol) in 1,4 dioxane (1.0 ml), was added Pd2(dba)3 (0.26 g, 0.28 mmol) and the resulting reaction mixture was irradiated to 120 C. in the microwave for 30 minutes. The reaction was allowed to cool to room temperature and was diluted with EtOAc and the reaction was diluted with EtOAc and palladium scavenger (Silicycle DMT) was added and mixture was stirred for 30 minutes, then filtered through a sintered funnel. The filtrate was washed with water, brine, dried (MgSO4), and concentrated to afford filtered and stripped to 2,5-difluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (2.4 g, 9.4 mmol): LCMS(m/z) 255.1 (MH+), tR=0.95 minute; LCMS(m/z) 174.0 (MH+, boronic acid), tR=0.3 minute. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In tetrahydrofuran; at 40 - 65℃; for 1h;Inert atmosphere; | EXAMPLE 2 Preparation of dichloro(3-phenyl-1H-inden-1-ylidene)bis-(tricyclohexylphosphine)ruthenium(II) (according to the invention; c = 0.5 mol/l) A one liter glass reactor with condenser and stirrer is filled with argon and thereafter with 500 ml of THF. The solvent is warmed up to 40C. Then 221.7 g (250 mmol, 1 eq.) of (PPh3)2Cl2Ru(3-phenylindenylidene) (Umicore AG & Co. KG, Hanau) and 155 g (98.1% purity, 540 mmol, 2.16 eq.) of tricyclohexylphosphine (PCy3, Aldrich) are added successively with stirring. The reaction mixture is stirred under reflux (65C) for 1 h during which time the product precipitates in form of dark red crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | A mixture of ruthenium(III)chloride hydrate (8.05 g ≈0.03 mol) and triphenylphosphane (39.3 g, 0.15 mol) wasplaced in a Schlenk flask, which was purged with argon. Methanol (300 mL) wasadded into the flask and the resulting mixture was heated at reflux for 4 h undercontinuous stirring. After cooling of the reaction mixture to rt, the precipitate wasfiltered off, washed with Et2O (3 × 100 mL) and air-dried to give 30.93 g of theWilkinson complex as black powder.Dichloro(3-phenyl-1H-inden-1-ylidene)bis(tricyclohexylphosphane)ruthenate(8). A solution of RuCl2(PPh3)3-4 (40.0 g, ≈41.7 mmol) and 1,1-diphenyl-2-propyn-1-ol(10.4 g, 50.1 mmol) in abs. THF (300 mL) was placed into a Schlenk flask under anargon atmosphere. A 5.4 M solution of HCl in dioxane (6.2 mL, 33.4 mmol) wasadded and then the mixture was heated at reflux for 30 min under continuous stirringand an argon atmosphere. After cooling to rt, around 50% of mixture volume wasevaporated under reduced pressure. Acetone (280 mL) and tricyclohexylphosphane25.7 g (91.9 mmol) were added to the residue and the resulting suspension wasstirred until thickening (≈0.5 h). After holding at -20 for 10 h the precipitate wasfiltered off and washed sequentially by methanol (2 × 80 mL), acetone (2 × 100 mL)and hexane (100 mL), then dried under vacuum at rt to give indenylidene-rutheniumcomplex 8 in 94% yield (36.3 g, 39.2 mmol) as red-brown powder.Complex 8 can be obtained by an analogical procedure in 90% yield (34.8 g)using absolute dioxane as a solvent instead absolute THF. |