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Chemical Structure| 2622-14-2 Chemical Structure| 2622-14-2

Structure of Tricyclohexylphosphine
CAS No.: 2622-14-2

Chemical Structure| 2622-14-2

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Product Details of [ 2622-14-2 ]

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

Safety of [ 2622-14-2 ]

GHS Pictogram:
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

Computational Chemistry of [ 2622-14-2 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

13.59 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

4.08
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

5.37
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

6.47
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

5.61
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

5.8
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

5.47

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-4.76
Solubility 0.00483 mg/ml ; 0.0000172 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-5.41
Solubility 0.00109 mg/ml ; 0.0000039 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-4.3
Solubility 0.0142 mg/ml ; 0.0000505 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

Yes
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-4.2 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

1.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

1.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

2.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

4.25

Application In Synthesis of [ 2622-14-2 ]

* 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.

  • Downstream synthetic route of [ 2622-14-2 ]

[ 2622-14-2 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 172222-30-9 ]
  • [ 548490-77-3 ]
  • C37H66Cl2NO3P2Ru [ No CAS ]
  • C43H75Cl2NO3P2Ru [ No CAS ]
  • [ 2622-14-2 ]
YieldReaction ConditionsOperation 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.
  • 2
  • [ 113978-91-9 ]
  • [ 2622-14-2 ]
  • [ 998-40-3 ]
  • tricyclohexylphosphine tetrafluoroborate [ No CAS ]
  • 3
  • [ 998-40-3 ]
  • tricyclohexylphosphine tetrafluoroborate [ No CAS ]
  • [ 113978-91-9 ]
  • [ 2622-14-2 ]
  • 4
  • [ 1001-26-9 ]
  • [ 19472-74-3 ]
  • [ 3375-31-3 ]
  • [ 2622-14-2 ]
  • 3-(ethoxy-hydroxy-methylene)-3H-indene-1-carbonitrile, sodium salt [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 5
  • [ 1001-26-9 ]
  • [ 51655-39-1 ]
  • [ 3375-31-3 ]
  • [ 2622-14-2 ]
  • [ 474024-32-3 ]
YieldReaction ConditionsOperation 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.
  • 7
  • (1,8-naphthylene)P(S)NiPr2 [ No CAS ]
  • [ 52522-40-4 ]
  • [ 67-66-3 ]
  • [ 2622-14-2 ]
  • rac-[(Pd(μ2-κS:κ2P,C-(1,8-naphthylene)P(S)N(iPr)2)(PCy3))2]*3/4CHCl3 [ No CAS ]
  • 8
  • PD2 [ No CAS ]
  • bis(pinacolato)diboron [ No CAS ]
  • [ 1262198-07-1 ]
  • [ 1269233-07-9 ]
  • [ 2622-14-2 ]
  • [ 1269233-08-0 ]
YieldReaction ConditionsOperation 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.
  • 9
  • bis(pinacolato)diboron [ No CAS ]
  • [ 1269232-99-6 ]
  • [ 2622-14-2 ]
  • [ 1269233-00-2 ]
YieldReaction ConditionsOperation 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.
  • 10
  • dichloro(3-phenyl-1H-indene-1-ylidene)(bistriphenylphosphine)ruthenium(II) [ No CAS ]
  • [ 2622-14-2 ]
  • [ 250220-36-1 ]
YieldReaction ConditionsOperation 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.
  • 11
  • ruthenium(III) chloride trihydrate [ No CAS ]
  • [ 3923-52-2 ]
  • [ 2622-14-2 ]
  • [ 250220-36-1 ]
YieldReaction ConditionsOperation 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.
 

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