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Chemical Structure| 51173-05-8

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Product Details of [ 51173-05-8 ]

CAS No. :51173-05-8
Formula : C5H4FNO
M.W : 113.09
SMILES Code : FC1=CN=C(C=C1)O
MDL No. :MFCD03092918
InChI Key :KLULSYPVWLJZAO-UHFFFAOYSA-N
Pubchem ID :2762864

Safety of [ 51173-05-8 ]

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

Computational Chemistry of [ 51173-05-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 26.22
TPSA ?

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

33.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.26
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

0.93
Log Po/w (WLOGP)?

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

1.35
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.

0.62
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

1.39
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.11

Water Solubility

Log S (ESOL):?

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

-1.68
Solubility 2.35 mg/ml ; 0.0208 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.21
Solubility 6.94 mg/ml ; 0.0614 mol/l
Class?

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

Very 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

-1.67
Solubility 2.42 mg/ml ; 0.0214 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

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

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.

-6.33 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)

1.45

Application In Synthesis of [ 51173-05-8 ]

* 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 [ 51173-05-8 ]

[ 51173-05-8 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 51173-05-8 ]
  • [ 136888-20-5 ]
YieldReaction ConditionsOperation in experiment
43% With sulfuric acid; nitric acid; at 85℃;Cooling with ice; a) 5-Fluoro-3-nitropyridin-2-ol A mixture of concentrated sulphuric acid (1 mL) and fuming nitric acid (1 mL) was added dropwise to a stirred, cooled (ice-bath) mixture of 5-fluoropyridin-2-ol (1.20 g, 10.6 mmol) and concentrated sulphuric acid (2.7 mL). The mixture was warmed to ambient temperature and then to 85 C. After 2 hours, the mixture was cooled and poured onto ice-water. The precipitate was filtered and dried to give the title compound (0.72 g, 43%) as a yellow solid. LRMS (m/z): 157 (M-1)+. 1H NMR delta (300 MHz, DMSO-d6): 8.28 (s, 1H), 8.67 (s, 1H).
43% With sulfuric acid; nitric acid; at 85℃; for 2h;Cooling with ice; 5-Fluoro-2-methoxypyridin-3 -amine a) 5-Fluoro-3-nitropyridin-2-olA mixture of concentrated sulphuric acid (1 mL) and fuming nitric acid (1 mL) was added dropwise to a stirred, cooled (ice-bath) mixture of 5-fluoropyridin-2-ol (1 .20 g, 10.6 mmol) and concentrated sulphuric acid (2.7 mL). The mixture was warmed to ambient temperature and then heated to 85 C. After 2 hours, the mixture was cooled and poured onto ice-water. The precipitate was filtered and dried to give the title compound (0.72 g, 43%) as a yellow solid.LRMS (m/z): 157 (M-1 )+.1H NMR delta (300 MHz, DMSO-d6): 8.28 (s, 1 H), 8.67 (s, 1 H).
40% With sulfuric acid; nitric acid; at 28 - 65℃; for 2.75h; To a solution of 5-fluoro-2-hydroxypyridine (200 mg, 1.77 mmol) in concentrated sulfuric acid (900 mul) was added, dropwise over 15 minutes, a premixed solution of concentrated sulfuric acid (900 mul) and fuming nitric acid (170 mul). The internal temperature rose by up to 280C. The reaction mixture was then heated at 650C for 2.5 hours. The cooled mixture was poured onto ice-water, and the pH of the mixture was adjusted to 2.5 with sodium carbonate. It was then extracted with ethyl acetate (2 x 25 ml). The aqueous layer was concentrated and extracted again with a mixture of tetrahydrofuran (25 ml) and ethyl acetate (25 ml). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield the title compound (112 mg, 40%) as a solid. 1H NMR (400MHz, DMSO-D6): delta 8.22 (dd, 1 H), 8.60 (dd, 1 H); LRMS APCI" m/z 157 [M-H]'.
With sulfuric acid; nitric acid; In water; at 65 - 80℃; for 1h; The solid from above containing (4-80) was divided in 4 batches and treated with H2SO4 and fuming HNO3 as shown below. The amounts used were: Compound 4-80 was dissolved in sulfuric acid (the larger amounts indicated above) at rt and then heated to 65 C. A preformed solution of fuming nitric acid and sulfuric acid (the smaller amount indicated above) was added dropwise. The temperature was kept between 65 C. and 80 C. (rxn is exothermic and although the bath is at 65 C., temperature goes higher, usually 75, sometimes 80 C.). After the addition was complete, the reaction mixture was heated at 65 C. for an additional hr. The reaction mixture was then cooled to rt and poured in a flask containing ice) (20 g of ice/gr compound, evolution of gas occurred). A solid precipitated out and it was collected by filtration (1HNM? showed 4-80 and something else (discarded)). [1493] The aqueous layer was extracted with AcOEt several times (3-5) and concentrated on a rotary evaporator under vacuum to afford a solid that was triturated with ether to afford 5-80 as a bright yellow solid. A total of 117 g of desired product was collected in the first crop (27% yield from diazonium salt). A portion did not crystallize: this oil was triturated with MeOH and Et2O to afford 3.6 g of 5-80; another precipitation from the mother liquid afforded an additional 6.23 g of the desired product 5-80 [1494] Total:117.0+3.6+6.23 =126.83. 30.4%). Yield for 3 steps (decomposition of diazonium salt; deprotection and nitration). [1495] Analytical data from Notebook: 53877-115: 1HNMR(delta, MeOD): 8.56-8.27 (dd, J=7.5, 3.3 Hz, 1H), 8.01 (d, J=3.3 Hz, 1H); LC/MS(M+1)+=158.9; rt=0.15 min. [1496] Note: A portion of the aqueous acidic solution was taken and neutralized with Na2CO3 until effervescence stopped and then it was extracted with AcOEtA different product was obtained. No desired product in these extracts.
With sulfuric acid; nitric acid; at 20 - 80℃; for 1h; Intermediate 3 was dissolved in sulfuric acid (the larger amounts indicated above) at rt and then heated to 65 C. A preformed solution of fuming nitric acid and sulfuric acid (the smaller amount indicated above) was added dropwise. The temperature was kept between 65 C. and 80 C. (rxn is exothermic and although the bath is at 65 C., temperature goes higher, usually 75, sometimes 80 C.). After the addition was complete, the reaction mixture was heated at 65 C. for an additional hr. The reaction mixture was then cooled to rt and poured in a flask containing ice) (20 g of ice/gr compound, evolution of gas occurred). A solid precipitated out and it was collected by filtration (1HNM? showed intermediate 4 and something else (discarded)). The aqueous layer was extracted with AcOEt several times (3-5) and concentrated on a rotary evaporator under vacuum to afford a solid that was triturated with ether to afford intermediate 4 as a bright yellow solid. A total of 117 g of desired product was collected in the first crop (27% yield from diazonium salt). A portion did not crystallize: this oil was triturated with MeOH and Et2O to afford 3.6 g of intermediate 4; another precipitation from the mother liquid afforded an additional 6.23 g of the desired product intermediate 4. Total: 117.0+3.6+6.23=126.83. 30.4%). Yield for 3 steps (decomposition of diazonium salt; deprotection and nitration). Analytical data from Notebook: 53877-115: 1HNMR(delta, MeOD): 8.56-8.27 (dd, J=7.5, 3.3 Hz, 1H), 8.01 (d, J=3.3 Hz, 1H); LC/MS(M+1)+=158.9; rt=0.15 min.
With sulfuric acid; nitric acid; In water; at 65 - 80℃; Compound 4-80 was dissolved in sulfuric acid (the larger amounts indicated above) at rt and then heated to 65 C. A preformed solution of fuming nitric acid and sulfuric acid (the smaller amount indicated above) was added dropwise. The temperature was kept between 65 C. and 80 C. (rxn is exothermic and although the bath is at 65 C., temperature goes higher, usually 75, sometimes 80 C.). After the addition was complete, the reaction mixture was heated at 65 C. for an additional hr. The reaction mixture was then cooled to rt and poured in a flask containing ice) (20 g of ice/gr compound, evolution of gas occurred). A solid precipitated out and it was collected by filtration (1HNM showed 4-80 and something else (discarded)). The aqueous layer was extracted with AcOEt several times (3-5) and concentrated on a rotary evaporator under vacuum to afford a solid that was triturated with ether to afford 5-80 as a bright yellow solid. A total of 117 g of desired product was collected in the first crop (27% yield from diazonium salt). A portion did not crystallize: this oil was triturated with MeOH and Et2O to afford 3.6 g of 5-80; another precipitation from the mother liquid afforded an additional 6.23 g of the desired product 5-80. Total: 117.0+3.6+6.23=126.83. 30.4%). Yield for 3 steps (decomposition of diazonium salt; deprotection and nitration). Analytical data from Notebook: 53877-115: 1HNMR(delta, MeOD): 8.56-8.27 (dd, J=7.5, 3.3 Hz, 1H), 8.01 (d, J=3.3 Hz, 1H); LC/MS(M+1)+=158.9; rt=0.15 min. Note: A portion of the aqueous acidic solution was taken and neutralized with Na2CO3 until effervescence stopped and then it was extracted with AcOEt A different product was obtained. No desired product in these extracts.

  • 2
  • [ 51173-05-8 ]
  • [ 136888-21-6 ]
  • 3
  • [ 51173-05-8 ]
  • [ 136888-20-5 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; nitric acid; In water; at 85℃; for 1h; In Step A, compound zzl' (1.2 g, 0.01 mol) was dissolved in sulfuric acid (2.7 mL) at room temperature. Premixed fuming nitric acid (1 mL) and sulfuric acid was added dropwise at 5-10 C. to the solution of compound zzl'. The reaction mixture was then heated at 85 C. for 1 hour, then was cooled to room temperature and poured into ice (20 g). The yellow solid precipitate was collected by filtration, washed with water and air dried to provide 1.01 g of compound zz2'.
With nitric acid;sulfuric acid; Intermediate 4,4-fluoro-7-bromo-6-azaindole, was prepared according to the following scheme: [CHEMMOL-00081] [0364] A) fuming HNO3, H2SO4; [0365] B) POBr3/DMF, 110 C.; [0366] C) vinylmagnesium bromide, THF, -78 C. -20 C. [0367] Intermediate 4 was isolated as a brownish solid. MS m/z: (M+H)+ calcd for C7H5BrFN2: 214.96; found 214.97. HPLC retention time: 1.28 minutes (column G).
 

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