161957-59-1|1-(3-Chloro-2-fluorophenyl)ethanone| Ambeed

CAS No. :	161957-59-1
Formula :	C₈H₆ClFO
M.W :	172.58
SMILES Code :	CC(C1=CC=CC(Cl)=C1F)=O
MDL No. :	MFCD00106165
InChI Key :	ZHDLNEIXOUIAQO-UHFFFAOYSA-N
Pubchem ID :	11116531

Safety of [ 161957-59-1 ]

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

Computational Chemistry of [ 161957-59-1 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.12
Num. rotatable bonds	1
Num. H-bond acceptors	2.0
Num. H-bond donors	0.0
Molar Refractivity	41.6
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	17.07 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.69
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	2.33
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.1
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.	2.79
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	3.21
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.62

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.72
Solubility	0.332 mg/ml ; 0.00193 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.	-2.33
Solubility	0.812 mg/ml ; 0.0047 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	-3.62
Solubility	0.041 mg/ml ; 0.000238 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	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.	-5.7 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)	1.38

Application In Synthesis of [ 161957-59-1 ]

* 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 [ 161957-59-1 ]

[ 161957-59-1 ] Synthesis Path-Downstream 1~54

1
[ 75-77-4 ]
[ 161957-55-7 ]
[ 161957-59-1 ]

References: [1]Tetrahedron Letters,1995,vol. 36,p. 881 - 884.

2
[ 75-36-5 ]
1-chloro-2-fluoro-3-(trimethylsilyl)benzene [ No CAS ]
[ 161957-59-1 ]

References: [1]Tetrahedron Letters,1995,vol. 36,p. 881 - 884.
[2]Bulletin de la Societe Chimique de France,1996,vol. 133,p. 133 - 141.

3
[ 917-54-4 ]
[ 161957-55-7 ]
[ 161957-59-1 ]

References: [1]Bulletin de la Societe Chimique de France,1996,vol. 133,p. 133 - 141.

4
[ 110-91-8 ]
[ 161957-59-1 ]
1-(3-chloro-2-morpholin-4-yl-phenyl)-ethanone [ No CAS ]
[ 591742-62-0 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1725 - 1728.

5
[ 161957-59-1 ]
1-(2-fluoro-3-morpholin-4-yl-phenyl)-ethylamine [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1725 - 1728.

6
[ 161957-59-1 ]
1-(2-fluoro-3-morpholin-4-yl-phenyl)-ethanone oxime [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1725 - 1728.

7
[ 348-51-6 ]
[ 161957-59-1 ]

References: [1]Bulletin de la Societe Chimique de France,1996,vol. 133,p. 133 - 141.
[2]Tetrahedron Letters,1995,vol. 36,p. 881 - 884.

8
[ 161957-59-1 ]
2-bromo-1-(3-chloro-2-fluorophenyl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bromine; In 1,4-dioxane; at 20℃;	To a solution of <strong>[161957-59-1]1-(3-chloro-2-fluoro-phenyl)-ethanone</strong> (8.5 g, commercially available) in1 ,4-dioxane (50 ml.) Br2 (7.79 g) was added and the mixture was stirred at RT for overnight. Water was added to the mixture and the compound extracted with EA (30 ml. X 3). The organic phase was dried, filtered and the solvent evaporated under vacuum. The crude was purified by column to give the title compound (10.2 g).1H NMR (CDCI3) delta: 4.44 (2H, s), 7.15-7.20 (1 H, m), 7.62-7.66 (1 H, t), 7.79-7.85 (1 H, t).

References: [1]Patent: WO2009/130232,2009,A1 .Location in patent: Page/Page column 60-61.

9
[ 2365-48-2 ]
[ 161957-59-1 ]
[ 1415968-75-0 ]

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 15 - 30.

10
[ 161957-59-1 ]
[ 1415968-58-9 ]

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 15 - 30.

11
[ 161957-59-1 ]
[ 1415968-59-0 ]

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 15 - 30.

12
[ 161957-59-1 ]
[ 752135-41-4 ]

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 15 - 30.

13
3-(morpholinosulfonyl)benzohydrazide [ No CAS ]
[ 161957-59-1 ]
[ 1423715-10-9 ]

Yield	Reaction Conditions	Operation in experiment
22 mg	With acetic acid; In methanol; at 120℃; for 0.5h;Microwave irradiation;	1-(3-Chloro-2-fluorophenyl)ethanone (20 mg, 0.116 mmol) and 3- (morpholinosulfonyl) benzohydrazide (33.1 mg, 0.116 mmol) waere dissolved in methanol (4 mL) in the presence of acetic acid as a catalyst, and the reaction mixture was heated via microwave irradiation to 120 C for 30 min. Following cooling, the solvent was removed by vacuum and the resulting crude material was purified by flash column chromatography (2% CH3OH/CH2CI2) affording the title compound (22 mg) as a solid. 1H NMR (400 MHz, CDCI3): delta 9.43 (s, 1 H), 8.37 (m, 1 H), 8.16 (m, 1 H), 7.87 (d, 1 H, J = 7.2 Hz), 7.65 (m, 1 H), 7.41 (m, 1 H), 7.10 (t, 1 H, J = 8.0 Hz), 3.71 (m, 4H), 2.95 (m, 4H), 2.38 (s, 3H). ESI-MS: 440.1 [M+H]+.

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 9496 - 9508.
[2]Patent: WO2013/25805,2013,A1 .Location in patent: Page/Page column 87.

14
titanium(IV) tetraethanolate [ No CAS ]
[ 146374-27-8 ]
[ 161957-59-1 ]
(R,E)-N-(1-(3-chloro-2-fluorophenyl)ethylidene)-2-methylpropane-2-sulfinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In tetrahydrofuran; ethyl acetate;	Step 1: (R,E)-N-(1-(3-chloro-2-fluorophenyl)ethylidene)-2-methylpropane-2-sulfinamide (18a) To a solution of <strong>[161957-59-1]1-(3-chloro-2-fluorophenyl)ethanone</strong> (5.60 g, 31.5 mmol) and (R)-2-methylpropane-2-sulfinamide (5.72 g, 47.2 mmol) in THF (50.0 mL) was added tetraethoxytitanium (16.50 mL, 79 mmol) and the overall bright yellow solution was heated at 70 C. for overnight. The reaction was slightly cooled with ice-water bath, then was added EtOAc (50 mL), NaHCO3 (10 mL), and brine (10 mL). The slurry was filtered through a short path of Celite and the wet cake was washed with EtOAc. The resulted bright yellow solution was phase separated, and the organic layer was concentrated to afford the title compound (8.3 g, 30.1 mmol, 96% yield) as a light yellow oil. This material was used in the next step without purification. MS m/z=276.0 [M+H]+. Calculated for C12H15ClFNOS: 275.77.

References: [1]Patent: US2014/249104,2014,A1 .Location in patent: Page/Page column.

15
[ 161957-59-1 ]
9H-fluoren-9-ylmethyl N-[(1S)-1-[3-chloro-2-(2-formylphenyl)sulfanylphenyl]ethyl]carbamate [ No CAS ]

References: [1]Patent: WO2017/72062,2017,A1 .

16
[ 161957-59-1 ]
N-[1-[3-chloro-2-[2-(hydroxymethyl)phenyl]sulfanylphenyl]ethylidene]-2-methylpropane-2-sulfinamide [ No CAS ]

References: [1]Patent: WO2017/72062,2017,A1 .

17
[ 161957-59-1 ]
N-[(1S)-1-[3-chloro-2-[2-(hydroxymethyl)phenyl]sulfanylphenyl]ethyl]-2-methylpropane-2-sulfinamide [ No CAS ]

References: [1]Patent: WO2017/72062,2017,A1 .

18
[ 161957-59-1 ]
[2-[2-[(1S)-1-aminoethyl]-6-chlorophenyl]sulfanylphenyl]methanol [ No CAS ]

References: [1]Patent: WO2017/72062,2017,A1 .

19
[ 161957-59-1 ]
9H-fluoren-9-ylmethyl N-[(1S)-1-[3-chloro-2-[2-(hydroxymethyl)phenyl]sulfanylphenyl]ethyl]carbamate [ No CAS ]

References: [1]Patent: WO2017/72062,2017,A1 .

20
[ 4521-31-7 ]
[ 161957-59-1 ]
1-[3-chloro-2-[2-(hydroxymethyl)phenyl]sulfanylphenyl]ethanone [ No CAS ]