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Chemical Structure| 80650-45-9

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Product Details of [ 80650-45-9 ]

CAS No. :80650-45-9
Formula : C11H10N2O
M.W : 186.21
SMILES Code : N1=CC(=CC=C1)OC2=CC=C(C=C2)N
MDL No. :MFCD07186369
InChI Key :ZSLIXJKSPVCNHZ-UHFFFAOYSA-N
Pubchem ID :3159631

Safety of [ 80650-45-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H317
Precautionary Statements:P280

Computational Chemistry of [ 80650-45-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 55.16
TPSA ?

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

48.14 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.8
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

1.87
Log Po/w (WLOGP)?

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

2.46
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.

1.13
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

1.8
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.81

Water Solubility

Log S (ESOL):?

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

-2.67
Solubility 0.394 mg/ml ; 0.00211 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.

-2.5
Solubility 0.585 mg/ml ; 0.00314 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

-3.92
Solubility 0.0222 mg/ml ; 0.000119 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

Yes
Log Kp (skin permeation)?

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

-6.11 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.

1.0 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)

2.04

Application In Synthesis of [ 80650-45-9 ]

* 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 [ 80650-45-9 ]
  • Downstream synthetic route of [ 80650-45-9 ]

[ 80650-45-9 ] Synthesis Path-Upstream   1~6

  • 1
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  • [ 80650-45-9 ]
YieldReaction ConditionsOperation in experiment
99% With palladium 10% on activated carbon; hydrogen In methanol at 20℃; Synthesis of compound 34-2 (0476) To the solution of 34-1 (2.0 g, 9.259 mmol) in MeOH (20 mL) was added 10percent Pd/C (0.2 g) purged with N2. Then H2 was added to remove N2. The mixture was stirred at room temperature overnight. After filtrated, the filtrate was concentrated to dryness affording 34-2 (1.7 g, 99percent) as brown solid.
98% With palladium 10% on activated carbon; hydrogen In methanol at 20℃; Step 4. 4-(Pyridin-3-yloxy) aniline. 3-(4-nitrophenoxy)pyridine (10.2 g, 47.18 mmol) was dissolved in 100 mL MeOH, followed by addition of Pd/C powder (10percentwt, 1.1 g). The reaction mixture was stirred at r.t. under H2 atmosphere overnight and filtered through Celite. The filtrate was concentrated to afford 4-(pyridin-3-yloxy)aniline (17.45 g, 98percent yield) as grey solid. LC-MS: m/z: 187 (M+H)+.
95% With hydrogen In tetrahydrofuran; methanol at 20℃; b) Compound 5 was hydrogenated at room temperature using PD/C in MEOH/THF. The reaction solution was filtered through kieselguhr and rinsed with MEOH, and the filtrate was subsequently evaporated. The residue was digested with diethyl ether, filtered off with suction, rinsed with diethyl ether and dried overnight at 40'C under reduced pressure. Yield : 37. 14 G (95percent) OF 6, PALE-BROWN CRYSTALS
95% With hydrogen In tetrahydrofuran; methanol at 20℃; The thus obtained nitro comound was hydrogenated at room temperature using Pd/C in MeOH/THF. The reaction solution was filtered through kieselguhr and rinsed with MeOH, and the filtrate was subsequently evaporated. The residue was digested with diethyl ether, filtered off with suction, rinsed with diethyl, ether and dried overnight at 40°C under reduced pressure. Yield : 37.14 g (95percent) of 5b, pale-brown crystals
95% With hydrogen In tetrahydrofuran; methanol at 20℃; Compound 5 is hydrogenated with Pd/C in [METHANOL/TETRAHYDROFURANE] at room temperature. The reaction mixture is filtered over kieselguhr, the residue washed with methanol and the filtrate evaporated. The residue is digested with diethyl ether, filtered by suction, washed with diethyl ether and dried in vacuum at 40 [°C] overnight to yield 37.14 g (95 percent) light brownish crystals of 6.
95% With hydrogen In tetrahydrofuran; methanol at 20℃; b) Compound 5 is hydrogenated at room temperature using Pd/C in MeOH/THF. The reaction solution is filtered through kieselguhr and rinsed with MeOH, and the filtrate is subsequently evaporated. The residue is digested with diethyl ether, filtered off with suction, rinsed with diethyl ether and dried overnight at 40°C under reduced pressure. Yield : 37.14 g (95percent) of 6, pale-brown crystals
95% With hydrogen In ethyl acetate for 3.5 h; A solution of 3- (4-nitrophenoxy)pyridine g, 23.13 mmol) in EtOAc (100 mL) in a 250 ml Parr bottle was purged with nitrogen. To this solution was added EtOAc-moistened 10percent Pd/C catalyst (500 mg, 10percent by weight). The reaction flask was placed in a Parr hygrogenation apparatus, purged with nitrogen (5x), evacuated, and then pressurized to 40 psi with hydrogen and shaken for 3.5 h. The reaction mixture was then purged with nitrogen, and filtered through a pad of Celite , rinsing with ethyl acetate (3x) and ethanol (3x). The filtrate was evaporated at reduced pressure to give a brown crystalline residue. The residue was stirred in diethyl ether at room temperature for 16 h and then filtered to provide 4.11 g (95percent) of the desired product as light brown crystals. (at)H-NMR (DMSO-d6) No. 8.21 (m, 2H), 7.30 (ddd, J = 8.4,4.6, 0.7 Hz, 1 H), 7.18 (ddd, J = 8.4, 2.9, 1.4 Hz, 1 H), 6.79 (d, J = 8.8 Hz, 2H), 6.58 (d, J = 9.0 Hz, 2H), 5.05 (br s, 2H) ; MS LC-MS [M+H]+ = 187, RT = 1.03 min.
36% With iron; ammonium chloride In tetrahydrofuran; methanol; water at 80℃; for 3 h; 4-(Pyridin-3-yl)oxy-l -nitrobenzene prepared in Step A was dissolved in the mixture of water (100 mL), tetrahydrofuran (100 mL) and methanol (100 mL). Iron powder (103 g, 1.84 mol) and ammonium chloride (99 g, 1.84 mol) were added thereto, and the mixture was stirred for 3 h at 80 °C using a mechanical stirrer. After completion of the reaction, the reaction mixture was filtered through a cellite, washed with methanol, and concentrated under reduced pressure. The solid thus obtained was filtered, washed with ether, and dried to give the title compound (17 g, Yield 36percent). Mass[M+H] : 186 (M+l)
36% With iron; ammonium chloride In tetrahydrofuran; methanol at 80℃; for 3 h; The compound thus obtained was dissolved using water (100ml), tetrahydrofuran (100ml) and methanol (100ml). Iron powder (103g, 1.84 mol) and ammonium chloride (99g, 1.84 mol) were added thereto, and the mixture was stirred using a mechanical stirrer for 3 h at 80 "C . After completion of the reaction, the reaction solution was filtered through a celite, washed with methanol, and concentrated.The resulting solid was filtered, washed with ether, and dried to give 4-(pyridin-3- yloxy)-phenylamine ( 17g, Yield 36percent).
36% With water; iron; ammonium chloride In tetrahydrofuran; methanol at 80℃; for 3 h; 4-(Pyridin-3-yl)oxy-1-nitrobenzene prepared in Step A was dissolved in the mixture of water (100 mL), tetrahydrofuran (100 mL) and methanol (100 mL). Iron powder (103 g, 1.84 mol) and ammonium chloride (99 g, 1.84 mol) were added thereto, and the mixture was stirred for 3 h at 80° C. using a mechanical stirrer. After completion of the reaction, the reaction mixture was filtered through a cellite, washed with methanol, and concentrated under reduced pressure. The solid thus obtained was filtered, washed with ether, and dried to give the title compound (17 g, Yield 36percent).

References: [1] Patent: US9138427, 2015, B2, . Location in patent: Page/Page column 309.
[2] Patent: WO2014/176258, 2014, A1, . Location in patent: Page/Page column 30.
[3] Patent: WO2004/85399, 2004, A1, . Location in patent: Page 168.
[4] Patent: WO2005/4863, 2005, A1, . Location in patent: Page/Page column 128.
[5] Patent: WO2004/19941, 2004, A1, . Location in patent: Page/Page column 154.
[6] Patent: WO2005/5389, 2005, A2, . Location in patent: Page 165.
[7] Patent: WO2005/110994, 2005, A2, . Location in patent: Page/Page column 81.
[8] Organic Letters, 2015, vol. 17, # 3, p. 426 - 429.
[9] Chemical Communications, 2017, vol. 53, # 95, p. 12814 - 12817.
[10] Patent: WO2009/25477, 2009, A1, . Location in patent: Page/Page column 57.
[11] Patent: WO2009/82152, 2009, A2, . Location in patent: Page/Page column 74.
[12] Patent: US2010/210647, 2010, A1, . Location in patent: Page/Page column 17.
[13] Yakugaku Zasshi, 1957, vol. 77, p. 944[14] Chem.Abstr., 1958, p. 2855.
[15] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 11, p. 1253 - 1256.
[16] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 22, p. 5473 - 5476.
[17] Patent: US2010/267708, 2010, A1, . Location in patent: Page/Page column 22.
[18] Patent: US2010/291533, 2010, A1, . Location in patent: Page/Page column 21.
[19] Patent: WO2009/117421, 2009, A2, . Location in patent: Page/Page column 207-208.
  • 2
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  • [ 80650-45-9 ]
References: [1] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 22, p. 5473 - 5476.
[2] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 11, p. 1253 - 1256.
[3] Patent: WO2014/176258, 2014, A1, .
[4] Organic Letters, 2015, vol. 17, # 3, p. 426 - 429.
[5] Chemical Communications, 2017, vol. 53, # 95, p. 12814 - 12817.
[6] Patent: WO2009/117421, 2009, A2, .
  • 3
  • [ 350-46-9 ]
  • [ 80650-45-9 ]
References: [1] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 22, p. 5473 - 5476.
[2] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 11, p. 1253 - 1256.
[3] Patent: WO2014/176258, 2014, A1, .
[4] Chemical Communications, 2017, vol. 53, # 95, p. 12814 - 12817.
  • 4
  • [ 636-98-6 ]
  • [ 80650-45-9 ]
References: [1] Organic Letters, 2015, vol. 17, # 3, p. 426 - 429.
  • 5
  • [ 109-00-2 ]
  • [ 350-46-9 ]
  • [ 80650-45-9 ]
References: [1] Patent: US9138427, 2015, B2, .
  • 6
  • [ 100-00-5 ]
  • [ 80650-45-9 ]
References: [1] Yakugaku Zasshi, 1957, vol. 77, p. 944[2] Chem.Abstr., 1958, p. 2855.
 

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