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Chemical Structure| 627899-90-5

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Product Details of [ 627899-90-5 ]

CAS No. :627899-90-5
Formula : C17H28BNO3
M.W : 305.22
SMILES Code : CC1(C)C(C)(C)OB(C2=CC=C(OCCCN(C)C)C=C2)O1
MDL No. :MFCD09702395
InChI Key :ONRJKPSMQGEPHV-UHFFFAOYSA-N
Pubchem ID :24229609

Safety of [ 627899-90-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 627899-90-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 22
Num. arom. heavy atoms 6
Fraction Csp3 0.65
Num. rotatable bonds 6
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 91.53
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

30.93 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

3.27
Log Po/w (WLOGP)?

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

2.32
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.

1.57
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

2.17
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.86

Water Solubility

Log S (ESOL):?

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

-3.6
Solubility 0.077 mg/ml ; 0.000252 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-3.59
Solubility 0.0777 mg/ml ; 0.000255 mol/l
Class?

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

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

-5.05
Solubility 0.00273 mg/ml ; 0.00000893 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

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)
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

Yes
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.

-5.84 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

0.0
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

0.0
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

0.0
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<0.0
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)

3.19

Application In Synthesis of [ 627899-90-5 ]

* 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 [ 627899-90-5 ]

[ 627899-90-5 ] Synthesis Path-Upstream   1~4

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YieldReaction ConditionsOperation in experiment
45%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1.16667 h; Inert atmosphere
Stage #2: at -78 - 20℃; for 24 h; Inert atmosphere
To a 100-mL flame-dried two necked flask was added M1 (3.0g, 11.6mmol) and freshly distilled THF (80mL). The resulting solution was cooled at−78°C and 8.7mL n-butyllithium (13.9mmol, 1.6M in hexane) was added over 10min under a nitrogen atmosphere. The mixture was stirred at−78°C for 1h. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.6g, 13.9mmol) was added rapidly to the solution, and the resulting mixture was slowly warmed to room temperature for 24h. The mixture was poured into 50mL water and extracted with CHCl3 (300mL). The combined organic layers were washed with brine and dried over anhydrous MgSO4. The solvent was removed by rotary evaporation, and the residue purified by column chromatography on silica gel (ethylacetate:dichloromethane as eluent) to obtain the product as a light-yellow oil (1.6g, yield: 45.0percent). 1H NMR (400MHz; CDCl3; Me4Si): δ=7.77 (d, 2H, J=8.8Hz), 6.90 (d, 2H, J=8.8Hz), 3.94 (t, 2H, J=6.4Hz), 2.46 (t, 2H, J=6.8Hz), 2.26 (s, 6H), 1.88 (m, 2H, J=6.8Hz) 1.25 (s, 12H). 13C NMR (100MHz; CDCl3; Me4Si): 161.57; 136.73; 113.41; 83.13; 74.40; 66.02; 54.09; 45.42; 27.43; 25.00. Anal. Calcd for: C17H28BNO3: C, 66.90; H, 9.25; N, 4.59. Found: C, 66.73; H, 9.23; N, 4.63. IR (KBr, cm−1): 2981, 2936, 2816, 2716, 1566, 1463, 1281, 1245.
45%
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 2 h; Inert atmosphere
Stage #2: at -78 - 20℃; for 26 h; Inert atmosphere
Dissolved in dry 30 Compound A 3g in a nitrogen atmosphere, THF, -78° C after the temperature was reduced to 2.2equivalent of n-butyllithium(nBuLi,Aldrich Co.) was slowly added. The reaction mixture was stirred at -78° C for 2 hours andthen, 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane,Aldrich) was added, and the mixture was stirred while the temperature gradually to room temperature after stirring at -78° Cfor 2 hours, the height for 24 hours. After the reaction was completed to extract the organic material with chloroform, to giveafter washing the column with water to obtain the compound B, 1.6 g (yield 45.0percent).
References: [1] Dyes and Pigments, 2015, vol. 113, p. 210 - 218.
[2] Patent: KR2015/122308, 2015, A, . Location in patent: Paragraph 0094; 0095; 0098; 0099.
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  • [ 76579-64-1 ]
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YieldReaction ConditionsOperation in experiment
42.4% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In 1,4-dioxane at 90℃; for 16 h; Inert atmosphere NrV-Dimethyl-3-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenoxy]propan-l- amine N,N-Dimethyl-3-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenoxy]propan-l -amine is available commercially from several suppliers including Apollo Scientific Ltd., Whitefield Rd, Bredbury, Stockport, Cheshire, SK6 2QR, UK. CAS number [627899-90- 5], catalogue number OR12268. Alternatively, it can be prepared as follows: A 1 : 1 complex of [l, -bis(diphenylphosphino)ferrocene]dichloropalladium(II) with dichloromethane (8.64 mg, 10.58 μιηο) was added to 3-(4-bromophenoxy)-N,N- dimethylpropan-1 -amine (546 mg, 2.12 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(l,3,2- dioxaborolane) (644 mg, 2.54 mmol) and potassium acetate (830 mg, 8.46 mmol) in 1,4- dioxane (6 mL) warmed to 90°C under nitrogen. The resulting suspension was stirred at 90 °C for 16 h. The reaction mixture was evaporated to dryness and re-dissolved in DCM (25 mL), and washed with water (20 mL). The organic layer was dried with a phase separating cartridge, filtered and evaporated to afford crude product. The crude product was purified by FCC, elution gradient 0 to 10percent MeOH in DCM. Pure fractions were evaporated to dryness to afford the desired material as a brown waxy solid (274 mg, 42.4 percent). NMR Spectrum: NMR (500MHz, CDCls) δ 1.33 (12H, s), 1.89 - 2.08 (2H, m), 2.32 (6H, s), 2.53 (2H, dt), 4.05 (2H, t), 6.86 - 6.91 (2H, m), 7.71 - 7.76 (2H, m). Mass Spectrum: m/z (ES+)[M+H]+ = 258.
42.3% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In 1,4-dioxane at 90℃; for 16 h; Inert atmosphere Dichloro [1,1 ‘-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct(0.063 g, 0.08 mmol) was added to 3-(4-bromophenoxy)-N,N-dimethylpropan-1-amine(2g, 7.75 mmol), 4,4,4’,4’,5 ,5 ,5’,5 ‘-octamethyl-2,2’-bi(1 ,3 ,2-dioxaborolane) (2.36 g, 9.30 mmol) and potassium acetate (3.04 g, 30.99 mmol) in 1,4-dioxane (35 mL) and the mixture degassed for 15 minutes. The resulting suspension was stirred at 90 °C for 16 hours under an inert atmosphere. The reaction mixture was evaporated to dryness, redissolved in DCM(25 mL), washed with water (20 mL) and the organic layer was dried with a phase separating cartridge, filtered and evaporated. The crude product was purified by flash silica chromatography, elution gradient 0 to 10percent MeOH in DCM, to afford the desired material as a brown oil (1.000 g, 42.3 percent) which solidified on standing. NMR Spectrum: ‘H NMR (400MHz, CDC13) ö 1.33 (12H, s), 1.96 - 2.07 (2H, m), 2.34(6H, s), 2.52 - 2.65 (2H, m), 4.04 (2H, t), 6.83 - 6.94 (2H, m), 7.68 - 7.78 (2H, m).Mass Spectrum: mlz (ES+) [M+H]+ = 306
References: [1] Patent: WO2017/76895, 2017, A1, . Location in patent: Page/Page column 46; 47.
[2] Patent: WO2019/57757, 2019, A1, . Location in patent: Page/Page column 56; 57; 58.
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References: [1] Patent: WO2017/76895, 2017, A1, .
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References: [1] Patent: WO2017/76895, 2017, A1, .
 

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