5-Phenyl-1,3-oxazole

Cat.NO.:A167353 Purity:97%

Product Details of [ 1006-68-4 ]

CAS No. :	1006-68-4
Formula :	C₉H₇NO
M.W :	145.16
SMILES Code :	O1C=NC=C1C1=CC=CC=C1
MDL No. :	MFCD00067074
InChI Key :	YPYPBEGIASEWKA-UHFFFAOYSA-N
Pubchem ID :	589311

Safety of [ 1006-68-4 ]

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

Computational Chemistry of [ 1006-68-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	11
Fraction Csp3	0.0
Num. rotatable bonds	1
Num. H-bond acceptors	2.0
Num. H-bond donors	0.0
Molar Refractivity	41.94
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	26.03 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.94
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	2.0
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.34
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.	1.06
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	2.52
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.97

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.67
Solubility	0.308 mg/ml ; 0.00212 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.	-2.17
Solubility	0.974 mg/ml ; 0.00671 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	-3.73
Solubility	0.0269 mg/ml ; 0.000185 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.	-5.77 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	1.0
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)	2.14

Application In Synthesis of [ 1006-68-4 ]

* 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 [ 1006-68-4 ]
Downstream synthetic route of [ 1006-68-4 ]

[ 1006-68-4 ] Synthesis Path-Upstream 1~2

1
[ 1006-68-4 ]
[ 62124-43-0 ]

Yield	Reaction Conditions	Operation in experiment
90.9%	Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 0.5 h; Stage #2: With hexachloroethane In tetrahydrofuran at 25℃; for 12 h;	[0819] to a solution of 5-phenyloxazole (800 mg, 5.51 mmol) in THF (10 ml) was added n-BuLi (2.5 m, 2.76 ml) drop-wise at -78 °C and stirred for 30 min, then hexachloroethane (1.96 g, 8.27 mmol) in THF (2 ml) was added, the reaction mixture was slowly warmed to 25 °C and stirred for 12 h. The mixture was poured into ice- water (20 ml) and extracted ethyl acetate (10 ml x 2), the organic phases were washed with brine (10 ml), dried over Na2SO4, filtered and concentrated, the residue was purified by silica gel column (petroleum ether: ethyl acetate = 10: 1) to give 114a (900 mg, yield: 90.9percent) as yellow oil. 1H NMR (400mhz, CDCl3) δ 7.58 (d, = 7.3 hz, 2h), 7.45 – 7.38 (m, 2h), 7.38 – 7.31 (m, 1h), 7.27 (s, 1h).
49%	Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 0.25 h; Stage #2: With hexachloroethane In tetrahydrofuran at -78 – 20℃; for 2 h;	[00208] To a round bottom flask was added 5-phenyloxazole (1.0 gm, 6.89 mmol) and THF (10 mL). The reaction was cooled to -78 °C. Then 2.5 M nBuLi (3.03 mL, 7.58 mmol) was added to the reaction at -78 °C. The reaction turned to deep red color. After 15 min, hexachloroethane (1.170 mL, 10.33 mmol) was added at -78 °C. The reaction was slowly warmed to rt over 2 hrs and then was poured onto ice. The resulting solution was extracted with EtO Ac (2 x 30ml). The combined EtO Ac layers were washed with saturated aqueous NaCl, dried over MgS0₄, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100percent EtO Ac/Hex to give the product, 2-chloro-5-phenyloxazole, (600 mg, 3.34 mmol, 49 percent yield) as a light pale liquid. Anal. Calcd. for C₉H₆C1N0 m/z 179.1, found: 180.1 (M+H)⁺; ‘H NMR (500 MHz, CDC1₃) δ ppm 7.60 (d, J=7.15 Hz, 2 H), 7.43 (t, J=7.42 Hz, 2 H), 7.38 – 7.33 (m, 1 H), 7.29 (s, 1 H); ¹³C NMR (126 MHz, CDCl₃) 5 ppm 153.78, 146.16, 129.01, 126.93, 124.03, 123.31.

References:

[1] Organic Letters, 2005, vol. 7, # 15, p. 3351 – 3354.

[2] Patent: WO2018/64119, 2018, A1, . Location in patent: Paragraph 0819.

[3] Patent: WO2013/12827, 2013, A1, . Location in patent: Paragraph 00208.

[4] Journal of Organic Chemistry, 1996, vol. 61, # 16, p. 5192 – 5193.

2
[ 1006-68-4 ]
[ 740806-67-1 ]

References:

[1] Journal of Organic Chemistry, 2008, vol. 73, # 8, p. 3303 – 3306.

[ 1006-68-4 ] Synthesis Path-Downstream 1~35

1
[ 1006-68-4 ]
[ 67242-59-5 ]
[ 96829-89-9 ]

Yield	Reaction Conditions	Operation in experiment
		a) According to reference (Synthesis 1984,1048-1050), to a solution of 5- [PHENYLOXAZOLE] (1.5 g, 10.3 mmol) in THF: diethyl ether (2: 1,50 mL) at-78 C is added n-butyl lithium (7.1 [ML] of 1.6 M solution in hexanes, 11.4 mmol). The reaction is stirred at-78 C for 30 minutes after which time a solution of N-methyl-2- pyridyl formamide (1.85 mL, 15.5 mmol) in THF (20 mL) is added. The reaction mixture is stirred at-78 C for 30 min and then at [25 C] for 14 hours. It is quenched by addition of water and extracted with ethyl acetate. The combined organic layers are washed with 10 % [HCI,] saturated sodium bicarbonate and brine before being dried over sodium sulfate and concentrated. The resulting oil is purified by column chromatography (5% ethyl acetate in hexanes) to afford 246 mg [OF 5-PHENYL-1,] 3- oxazole-2-carbaldehyde.
		A solution of <strong>[1006-68-4]5-phenyloxazole</strong> (0.192 g) in 2: 1 tetrahydrofuran/diethyl ether (7 mL) was cooled to -780C, and treated with n-butyl lithium (0.582 mL) dropwise under Argon. The mixture was stirred for 30 minutes at -780C, at this time a solution of N-methyl-N-(pyridin-2-yl) formamide (0.270 g) in tetrahydrofuran (2.6 mL) was added dropwise to the solution. After stirring at -780C for 30 minutes, the mixture was allowed to warm up to room temperature and stirring continued overnight. The mixture was quenched by the addition of water and extracted with ethyl acetate. The combined extracts were washed with 10% hydrochloric acid, saturated aqueous solution of sodium bicarbonate and brine, dried and concentrated in vacuo and purified by column chromatography on silica gel (10-50% ethyl acetate in hexane) to provide the title compound (0.016 g) with the following physical data.1H NMR (DMSO-d6): δ 9.72 (s, IH), 8.12 (s, IH), 7.88 (d, J = 7.02 Hz, IH), 7.60-7.49 (m, 4H); Mass data (APCI, Pos ): m/z 174 (M + H)+.

References: [1]Synthesis,1984,p. 1048 – 1050.
[2]Patent: WO2004/2977,2004,A1 .Location in patent: Page 26.
[3]Patent: WO2010/80864,2010,A1 .Location in patent: Page/Page column 175.

2
[ 1006-68-4 ]
[ 62124-43-0 ]

Yield	Reaction Conditions	Operation in experiment
90.9%		[0819] to a solution of 5-phenyloxazole (800 mg, 5.51 mmol) in THF (10 ml) was added n-BuLi (2.5 m, 2.76 ml) drop-wise at -78 °C and stirred for 30 min, then hexachloroethane (1.96 g, 8.27 mmol) in THF (2 ml) was added, the reaction mixture was slowly warmed to 25 °C and stirred for 12 h. The mixture was poured into ice- water (20 ml) and extracted ethyl acetate (10 ml x 2), the organic phases were washed with brine (10 ml), dried over Na2SO4, filtered and concentrated, the residue was purified by silica gel column (petroleum ether: ethyl acetate = 10: 1) to give 114a (900 mg, yield: 90.9percent) as yellow oil. 1H NMR (400mhz, CDCl3) delta 7.58 (d, = 7.3 hz, 2h), 7.45 – 7.38 (m, 2h), 7.38 – 7.31 (m, 1h), 7.27 (s, 1h).
49%		[00208] To a round bottom flask was added 5-phenyloxazole (1.0 gm, 6.89 mmol) and THF (10 mL). The reaction was cooled to -78 °C. Then 2.5 M nBuLi (3.03 mL, 7.58 mmol) was added to the reaction at -78 °C. The reaction turned to deep red color. After 15 min, hexachloroethane (1.170 mL, 10.33 mmol) was added at -78 °C. The reaction was slowly warmed to rt over 2 hrs and then was poured onto ice. The resulting solution was extracted with EtO Ac (2 x 30ml). The combined EtO Ac layers were washed with saturated aqueous NaCl, dried over MgS04, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100percent EtO Ac/Hex to give the product, 2-chloro-5-phenyloxazole, (600 mg, 3.34 mmol, 49 percent yield) as a light pale liquid. Anal. Calcd. for C9H6C1N0 m/z 179.1, found: 180.1 (M+H)+; ‘H NMR (500 MHz, CDC13) delta ppm 7.60 (d, J=7.15 Hz, 2 H), 7.43 (t, J=7.42 Hz, 2 H), 7.38 – 7.33 (m, 1 H), 7.29 (s, 1 H); 13C NMR (126 MHz, CDCl3) 5 ppm 153.78, 146.16, 129.01, 126.93, 124.03, 123.31.