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Chemical Structure| 34547-28-9

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Product Details of [ 34547-28-9 ]

CAS No. :34547-28-9
Formula : C8H9FN2O
M.W : 168.17
SMILES Code : NNC(=O)CC1=CC=C(F)C=C1
MDL No. :MFCD06655053
InChI Key :PFBNINAURUGQRR-UHFFFAOYSA-N
Pubchem ID :3771612

Safety of [ 34547-28-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 34547-28-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 41.88
TPSA ?

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

55.12 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

0.55
Log Po/w (WLOGP)?

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

0.78
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.

1.62
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

0.94
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.03

Water Solubility

Log S (ESOL):?

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

-1.4
Solubility 6.68 mg/ml ; 0.0397 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.

-1.28
Solubility 8.84 mg/ml ; 0.0525 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

-2.72
Solubility 0.323 mg/ml ; 0.00192 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.

-6.94 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

2.0 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)

1.41

Application In Synthesis of [ 34547-28-9 ]

* 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.

  • Downstream synthetic route of [ 34547-28-9 ]

[ 34547-28-9 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 459-04-1 ]
  • [ 34547-28-9 ]
YieldReaction ConditionsOperation in experiment
86% With hydrazine hydrate; triethylamine; In acetonitrile; for 3h;Reflux; General procedure: Aralkanoic acid chlorides 2a-g were synthesized by the reaction of aralkanoic acid 1a-g (1 mmol) in the presence of 1,2-dichloroethane (12 mL) solvent and phosphorous oxychloride(0.4 mL) chlorinating agent under reflux for 3hours. Then, the resulting solution was cooled to room temperature, and the solvent was removed under reduced pressureto afford aralkanoic acid chloride 2a-g, which was directly used in the next step without further purification. Acid chloride 2a-g was dissolved in acetonitrile (80 mL), addeddropwise to a solution containing hydrazine hydrate(1 mmol), TEA (0.5 mL) and acetonitrile (20 mL) and allowed to reflux for 3 hours with monitoring by TLC. After consumption of the starting material, the reaction mixture was cooled to room temperature. Evaporation of the solvent under reduced pressure yielded crude acid hydrazide 3a-g as a white solid on cooling, which was purified by column chromatography and crystallized in methanol [46].
69% With hydrazine; In dichloromethane; at 0℃; for 0.666667h; A cold (0 oC) solution of hydrazine (4. 5 ML, 144 mmol) in dichloromethane (50 mL) was treated with a dichloromethane solution of (4-fluorophenyl) acetyl chloride (1. 0 g, 5. 8 mmol). The resultant solution was stirred for 40 minutes and water was then added. The layers were separated and the aqueous layer was extracted with dichloromethane and the combined organics were dried over sodium sulfate. Filtration and concentration followed by purification by flash chromatography (5% methanol-dichloromethane gradient elution) provided 2- (4-FLUOROPHENYL) acetic hydrazide (673 mg, 69%) as a white solid. 1H NMR (DMSO-D6) : S 9. 18 (broad, 1 H), 7. 26 (dd, J= 8. 4, 5. 7 Hz, 2 H), 7. 09 (t, J= 8. 4 Hz, 2 H), 4. 21 (broad, 2 H), 3. 31 (s, 2 H) ; MS INTO 169 (M+1),
With hydrazine; Step 5: (7S)-3-(Benzyloxy)-N-[(4-fluorophenyl)acetyl]-5-methyl-7-phenyl-4;5,6,7- tetrahydropyrazolo[l,5-α]; A solution of (7S)-3-(benzyloxy)-5-methyl-7-phenyl-4,5,6,7-tetrahydropyrazolo[l,5- a]pyrazine-2-carboxylic acid (148 mg, 0.39 mmol), 2-(4-fluorophenyl)acetohydrazide (99 mg, 0.59 mmol; prepared from 4-fluorophenyl acetyl chloride and hydrazine in a manner similar to that described in J. Heterocyclic Chemistry, 1977, 14, 1123), EDC (113 mg, 0.59 mmol), HOBT (79 mg, 0.59 mmol) and triethylamine (82 μL, 0.59 mmol) in DMF (1 mL) was stirred at room temperature for 1 hour. The DMF was removed in vacuo and the residue was partitioned between water and ethyl acetate, adjusting to a pH of 3 using IN HCl. The layers were then separated and the aqueous layer was extracted with more ethyl acetate (2 x 10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure to give the product as white solid. lH NMR (400 MHz, d6-DMSO) δ 10.2 (s, IH), 9.84 (s, IH), 7.98 (dd, J = 8.4 Hz, IH), 7.72 (d, J = 8.4 Hz, IH), 7.56-7.51 (m, 2H), 7.43- 7.34 (m, 6H), 7.14 (t, J = 8.9 Hz, 2H), 6.97 (d, J = 6.1 Hz, 2H), 5.79 (m, IH), 5.34 (AB quartet, J = 10.9 Hz, 2H), 4.23 (dd, J = 13, 4.7 Hz, IH), 3.84 (dd, J = 13.7, 3.7 Hz, IH), 3.52 (s, 2H), and 2.92 (s, 3H). ES MS (M+l) = 528.
With hydrazine; In dichloromethane; for 0.75h; To a solution of hydrazine (0.46 mL, 14.49 mmol, 2.5 equiv) in (¾(¾ (29 mL) was added slowly over 30 sec 2-(4- fluorophenyl)acetyl chloride (0.79 mL, 5.79 mmol, 1.0 equiv). Slight warming of the mixture and white precipitate were observed. After stirring 45 min, the mixture was poured into a saturated aqueous solution of NaHCC^ layered with (¾(¾ forming a thick emulsion. This emulsion was filtered through a medium glass frit to give a biphasic homogenous solution. This was extracted with CH2CI2 (x3). The combined CH2CI2 extracts were dried (Na2S04) and then concentrated in vacuo to provide the title compound (1.22 g, 124% yield) as a white solid. Source of extra mass is unclear as product is of high purity. Extra mass may reflect a measuring error of the acid chloride. XH NMR (400 MHz, CDC13) δ ppm 7.19 - 7.24 (m, 2 H), 6.99 - 7.07 (m, 2 H), 6.60 (s, 1 H), 3.85 (d, J=2.01 Hz, 2 H), 3.52 (s, 2 H); LCMS (ES+, (M+H)+) m/z 169.22.
With hydrazine hydrate; triethylamine; In acetonitrile; for 3h;Reflux; General procedure: Aralkanoic acid chlorides 2 were synthesized by the reaction ofaralkanoic acids 1 (1 mmol) in the presence of 1,2edichloroethane(12 mL) solvent and phosphorous oxychloride (0.4 mL) as chlorinatingagent under reflux for 3 h. Then, the resulting solution wascooled to room temperature, and the solvent was removed underreduced pressure to afford aralkanoic acid chlorides 2, which wasdirectly used in the next step without further purification. Aralkanoicacid chlorides 2 was dissolved in acetonitrile (80 mL), addeddrop wise to a solution containing hydrazine hydrate (1 mmol), TEA(0.5 mL) and acetonitrile (20 mL) and allowed to reflux for 3 h withmonitoring by TLC. After consumption of the starting material, thereaction mixture was cooled to room temperature. Evaporation ofthe solvent under reduced pressure yielded crude substituted aromaticacid hydrazides 3 as a white solid on cooling, which waspurified by column chromatography and crystallized on methanol.

 

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