35364-79-5|2-(3,4-Dichlorophenyl)ethanol| Ambeed

CAS No. :	35364-79-5
Formula :	C₈H₈Cl₂O
M.W :	191.06
SMILES Code :	OCCC1=CC(Cl)=C(Cl)C=C1
MDL No. :	MFCD00800673
InChI Key :	GITOMJDYNUMCOV-UHFFFAOYSA-N
Pubchem ID :	244558

Safety of [ 35364-79-5 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 35364-79-5 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.25
Num. rotatable bonds	2
Num. H-bond acceptors	1.0
Num. H-bond donors	1.0
Molar Refractivity	47.4
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	20.23 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.14
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.16
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.53
Log P_o/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.	3.03
Log P_o/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	3.27
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.83

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.29
Solubility	0.0987 mg/ml ; 0.000516 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.	-3.26
Solubility	0.106 mg/ml ; 0.000556 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	-3.87
Solubility	0.026 mg/ml ; 0.000136 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	No
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	Yes
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.	-5.22 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	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	0.0 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)	1.3

Application In Synthesis of [ 35364-79-5 ]

* 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.

Downstream synthetic route of [ 35364-79-5 ]

[ 35364-79-5 ] Synthesis Path-Downstream 1~55

1
[ 5807-30-7 ]
[ 35364-79-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With lithium aluminium tetrahydride; In tetrahydrofuran; at 20℃; for 5h;	To an ice-cold solution of 2-(3,4-dichlorophenyl)acetic acid (19.36 g, 94.42 mmol) in THF (200 mL) was added portionwise 97% LiAlH4 (5.54 g, 141.63 mmol). After the addition, the mixture was stirred at room temperature for 5 h. The resulting mixture was poured into ice-water (150 mL), and stirred for 0.5 h. The THF was removed under reduced pressure, then DCM (200 mL) was added. The organic layer was separated, washed with brine, dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (EtOAc/hexane = 1/5, V/V) to compound 6 as colourless oil (17.14 mg, 95%).
89%	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 2h;	A solution of LAH (69 mg, 1.8 mmol) in anhydrous THF was added dropwise to a solution of 2-(3,4-dichlorophenyl)acetic acid (250 mg, 1.2 mmol) in anhydrous THF at 0 C. The reaction mixture was stirred at room temperature for 2 h. Then cooled to 0 C, it was quenched with water and extracted with EA. The residue was dried over sodium sulfate and concentrated in vacuo. The desired compound (207 mg) was obtained. (yield : 89 %)1H NMR (400 MHz, CDCl3) delta 7.40 (d, J = 8.0 Hz, 1H), 7.37 (s, 1H), 7.10 (dd, J = 8.0, 2.0 Hz, 1H), 3.89 (t, J = 6.4 Hz, 2H), 2.85 (t, J = 6.4 Hz, 2H).
	With lithium aluminium tetrahydride; In diethyl ether; for 12h;Heating / reflux;	3,4-Dichlorophenethyl alcohol: To a solution of lithium aluminum hydride (7.79 g, 195 mmol) in anhydrous diethyl ether (435 mL) was added slowly as a powder, via a solid dropping funnel, 3,4-dichlorophenyl acetic acid (27.20 g, 130 mmol). When the addition was completed, the reaction mixture was refluxed for 12 hours. The reaction was quenched by cautious addition of saturated sodium sulfate aqueous solution (20 mL), the resulting insoluble was then filtered off and the filtrate was concentrated in vacuo to yield 25.09 g of the desired alcohol.

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2818 - 2841.
[2]Journal of Medicinal Chemistry,1990,vol. 33,p. 3100 - 3110.
[3]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 5420 - 5423.
[4]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 1168 - 1172.
[5]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 756 - 760.
[6]Journal of the American Chemical Society,1956,vol. 78,p. 5612.
[7]Journal of Medicinal Chemistry,1998,vol. 41,p. 358 - 378.
[8]Medicinal Chemistry Research,1999,vol. 9,p. 213 - 222.
[9]Patent: EP1087934,2004,B1 .Location in patent: Page 25.
[10]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 6463 - 6480.
[11]Journal of Medicinal Chemistry,2016,vol. 59,p. 7212 - 7222.
[12]Journal of Enzyme Inhibition and Medicinal Chemistry,2018,vol. 33,p. 1460 - 1471.

2
[ 21581-45-3 ]
[ 35364-79-5 ]

References: [1]Patent: DE1109700,1959, .

3
[ 35364-79-5 ]
[ 21085-57-4 ]

References: [1]Journal of Medicinal Chemistry,1970,vol. 13,p. 1051 - 1057.
[2]Patent: DE1109700,1959, .

4
[ 6725-45-7 ]
[ 35364-79-5 ]

References: [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 1108 - 1118.

5
[ 124-63-0 ]
[ 35364-79-5 ]
[ 81156-65-2 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; at 0℃;	2-(3,4-Dichlorophenyl)ethanol (150 mg, 0.769 mmol) was dissolved in(DCM (3 mL) and when the temperature was cooled down at O C methanesulfonyl chloride (0.066 mL, 0.846 mmol) was slowly added leaving the mixture under stirring overnight. Next morning HPLC showed completion. Volatiles were removed under vacuum and the mixture was treated with water and EtOAc. Organic layers were dried over Na2SOf filtered and the solvent removed under vacuum to obtain 200 mg of the desired compound as colourless oil that was used in the next step without further purification.
	With triethylamine; In dichloromethane; at 0 - 20℃; for 0.6h;Inert atmosphere;	[00318] MsCl (2.40 g, 20.92 mmol) was added to a solution of <strong>[35364-79-5]2-(3,4-dichlorophenyl)ethanol</strong> (1.00 g, 5.23 mmol) and TEA (1.59 g, 15.69 mmol, 2.17 mL) in dry DCM (10.00 mL) dropwise under N2 atmosphere for 5 minutes. It was stirred at 0 to 20 C for 0.6 h. The solution was diluted with water and extracted with ethyl acetate. The organic phase was washed with water (100 mL x 2) and brine (100 mL), dried (Na2S04), filtered and concentrated in vacuo to yield the crude product. It was used for the next step directly.

References: [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 3100 - 3110.
[2]Journal of Medicinal Chemistry,1989,vol. 32,p. 1108 - 1118.
[3]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 6463 - 6480.
[4]Patent: WO2009/141399,2009,A1 .Location in patent: Page/Page column 47-48.
[5]Patent: WO2018/191146,2018,A1 .Location in patent: Paragraph 00318.

6
[ 35364-79-5 ]
[ 114686-64-5 ]

References: [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 358 - 378.
[2]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 756 - 760.

7
[ 52909-94-1 ]
[ 60-29-7 ]
lithium borate [ No CAS ]
[ 1475-11-2 ]
[ 35364-79-5 ]

References: [1]Journal of the American Chemical Society,1956,vol. 78,p. 5612.

8
[ 52909-94-1 ]
[ 64-17-5 ]
platinum [ No CAS ]
[ 1475-11-2 ]
[ 35364-79-5 ]

References: [1]Journal of Organic Chemistry,1957,vol. 22,p. 93.

Yield	Reaction Conditions	Operation in experiment
89%	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 2h;	General procedure: 1.0M lithium aluminum hydride (LAH; 3.4 mL, 3.4 mmol) dissolved in tetrahydrofuran (THF) 2- (4-methyl-3- (trifluoromethyl) phenyl) acetic acid (2-I-1; 500 mg, 2.3 mmol) dissolved in tetrahydrofuranAfter slowly adding to the mixture at 0 C, the mixture was stirred for 2 hours at room temperature.After the reaction was completed, the temperature was lowered to 0 C, methanol was slowly added, and then concentrated under reduced pressure to remove the solvent.The salt was dissolved with distilled water, lowered to pH 2-3 with 1N HCl aqueous solution, and extracted with ethyl acetate.Filtered after drying with anhydrous magnesium sulfate,The organic layer was concentrated under reduced pressure to obtain 448 mg (yield 96%) of the target compound (2-I-2).

10
[ 555-16-8 ]
[ 35364-79-5 ]
[ 220445-13-6 ]

Yield	Reaction Conditions	Operation in experiment
9.11 g (30%)	Zinc chloride; In benzene;	Step a) 6,7-Dichloro-1-(4-nitrophenyl)-isochromane 19.1 g (100 mM) of <strong>[35364-79-5]2-(3,4-dichlorophenyl)-ethanol</strong> [G. J. Park et al.: J. Org. Chem. 22, 93 (1957)] and 15.1 g (100 mM) of 4-nitrobenzaldehyde were dissolved in 300 ml of anhydrous benzene, then 13.6 g (100 mM) of anhydrous zinc chloride were added and dry hydrochloric acid gas was led into the stirred suspension for 4 hours. Then the process described under Examples 1-7, Step a) was applied. The crude product was recrystallized from ethanol. Yield 9.11 g (30%), m. p. 130-132 C.

References: [1]Bioorganic and Medicinal Chemistry,2000,vol. 8,p. 2127 - 2143.
[2]Patent: US6482819,2002,B1 .

11
[ 6725-44-6 ]
[ 35364-79-5 ]

References: [1]Medicinal Chemistry Research,1999,vol. 9,p. 213 - 222.

12
[ 35364-79-5 ]
[ 52516-52-6 ]

References: [1]Medicinal Chemistry Research,1999,vol. 9,p. 213 - 222.

13
[ 14199-15-6 ]
[ 35364-79-5 ]
{4-[2-(3,4-dichloro-phenyl)-ethoxy]-phenyl}-acetic acid methyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3434 - 3439.
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4085 - 4089.

14
C₁₁H₂₁NO₄S [ No CAS ]
[ 35364-79-5 ]
(1R,2R)/(1S,2S)-1-(2,4-dichlorophenethoxy)-2-(4-morpholinyl)cyclohexane [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2818 - 2841.

15
[ 35364-79-5 ]
[ 928776-10-7 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 756 - 760.

16
[ 35364-79-5 ]
4-[2-(3,4-Dichloro-phenyl)-ethyl]-6-(4-oxo-2-thioxo-thiazolidin-5-ylidenmethyl)-4H-benzo[1,4]oxazin-3-one [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 756 - 760.

17
[ 35364-79-5 ]
[ 900515-72-2 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4085 - 4089.
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3434 - 3439.

18
[ 35364-79-5 ]
[(S)-5-Amino-1-(5-{4-[2-(3,4-dichloro-phenyl)-ethoxy]-benzyl}-[1,2,4]oxadiazole-3-carbonyl)-pentyl]-carbamic acid benzyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4085 - 4089.

19
[ 35364-79-5 ]
[5-benzyloxycarbonylamino-6-(5-{4-[2-(3,4-dichloro-phenyl)-ethoxy]-benzyl}-[1,2,4]oxadiazol-3-yl)-6-hydroxy-hexyl]-carbamic acid tert-butyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4085 - 4089.

20
[ 35364-79-5 ]
[5-benzyloxycarbonylamino-6-(5-{4-[2-(3,4-dichloro-phenyl)-ethoxy]-benzyl}-[1,2,4]oxadiazol-3-yl)-6-oxo-hexyl]-carbamic acid tert-butyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4085 - 4089.

21
[ 35364-79-5 ]
C₃₆H₄₄Cl₂N₄O₈ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4085 - 4089.

22
[ 35364-79-5 ]
[ 885125-90-6 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3434 - 3439.

23
[ 35364-79-5 ]
[ 900515-79-9 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3434 - 3439.

24
[ 35364-79-5 ]
methyl N-2-(3,4-dichlorophenyl)ethyl-2-piperidylacetate [ No CAS ]

References: [1]Medicinal Chemistry Research,1999,vol. 9,p. 213 - 222.

25
[ 35364-79-5 ]
[ 220445-14-7 ]