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Chemical Structure| 344591-91-9

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Product Details of [ 344591-91-9 ]

CAS No. :344591-91-9
Formula : C5H6BF3N2O2
M.W : 193.92
SMILES Code : CN1N=C(C=C1B(O)O)C(F)(F)F
MDL No. :MFCD08701785
InChI Key :XPUNXPPXMANQGF-UHFFFAOYSA-N
Pubchem ID :12056713

Safety of [ 344591-91-9 ]

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

Computational Chemistry of [ 344591-91-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 5
Fraction Csp3 0.4
Num. rotatable bonds 2
Num. H-bond acceptors 6.0
Num. H-bond donors 2.0
Molar Refractivity 38.32
TPSA ?

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

58.28 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

0.09
Log Po/w (WLOGP)?

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

0.27
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.

-0.56
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

-1.02
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.24

Water Solubility

Log S (ESOL):?

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

-1.25
Solubility 10.9 mg/ml ; 0.056 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.

-0.87
Solubility 26.3 mg/ml ; 0.135 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

-0.58
Solubility 51.2 mg/ml ; 0.264 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

No
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.

-7.42 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

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)

2.16

Application In Synthesis of [ 344591-91-9 ]

* 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 [ 344591-91-9 ]

[ 344591-91-9 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 154471-65-5 ]
  • [ 344591-91-9 ]
YieldReaction ConditionsOperation in experiment
87% 2-methyl-5-trifluoromethyl-2H-pyrazole-3-boronic acid: <strong>[154471-65-5]1-methyl-3-trifluoromethyl-1H-pyrazole</strong> (1.00 g, 6.66 mmol) was dissolved in THF (25 mL) in an oven-dried round bottom flask and cooled to-78 C in an acetone/dry ice bath. 2.5 M n-butyl lithium/hexane (3.196 ml, 7.99 mmol) was added drop wise to the stirred solution followed by drop wise addition of triisopropyl borate (5.01 g, 26.64 mmol). The mixture was warmed to room temperature and stirred for three hours. The reaction mixture was adjusted to pH 6 with IN HCl solution followed by the removal of THF under vacuum. The aqueous phase was extracted with EtOAc (3x100 ml). The combined organic phase was washed with brine and dried over anhydrous MgS0(sub>4, filtered and evaporated to give 2-methyl-5-trifluoromethyl-2H-pyrazole-3-boronic acid (1.12 g, 5.80 mmol, 87 % yield) as a white solid: LCMS m/z (%) = 195 (M+H, 100). 1H NMR (400 MHz, DMSO-d6) delta: 8.37-8.40 (m, 2H), 7.57 (dd, J= 4.0 Hz, 1H), 4.06 (s, 3H).
  • 2
  • [ 121-43-7 ]
  • [ 154471-65-5 ]
  • [ 344591-91-9 ]
YieldReaction ConditionsOperation in experiment
64% Preparation 7[1 -Methyl-3-(trifluoromethyl)-1 H-pyrazol-5-yllboronic acidTo a stirred solution of 1 -methyl-3-(thfluoronnethyl)-1 H-pyrazole (1 .89 g, 12.6 mmol) in anhydrous tetrahydrofuran (20 ml_) under nitrogen cooled to -78C was added n- butyllithium (8.3 mL, 1 .6 M solution in hexanes, 13.2 mmol) slowly over 5 minutes. The resulting yellow solution was stirred at -78C for 1 hour and trimethyl borate (1 .56 mL, 13.9 mmol) was then added slowly. The reaction flask was covered in foil and allowed to warm to room temperature for 16 hours. The white solution was quenched with aqueous 1 M hydrogen chloride solution (10 mL) and stirred at room temperature for 1 .5 hours. The mixture was extracted with ethyl acetate (2 x 30 mL), dried with anhydrous magnesium sulphate and evaporated in vacuo to give an off-white foam (2.1 1 g). The foam was triturated with dichloromethane, filtered and dried in vacuo to afford the title compound as a white solid (1 .57 g, 64%).1H NMR (400 MHz, MeOH-d4): delta 4.04 (s, 3H), 6.89 (s, 1 H).LCMS Rt = 1 .1 1 minutes MS m/z 194 [MH]+ 192 [M-H]-,
With hydrogenchloride; diisopropylamine; In tetrahydrofuran; 4B Preparation of <strong>[154471-65-5]1-methyl-3-trifluoromethylpyrazol</strong>-5-yl-boronic acid A solution of <strong>[154471-65-5]1-methyl-3-trifluoromethylpyrazol</strong> (2 g) in 10 ml THF is cooled under an inert gas atmosphere to -78 C. A 2 M solution of LDA (9.75 ml) is added dropwise. The mixture is stirred to 10 C. for 1 h and cooled to -75 C. Trimethylborate (5.8 ml) is added and after stirring for 1 h at -75 C. the mixture is stirred overnight at ambient temperature. The resulting reaction solution is added to 10% hydrochloric acid (15 ml). The water phase is extracted 3 times with ethyl acetate and the combined organic phases are washed with water and a saturated sodium chloride solution. The organic phase is dried and evaporated and the residue is crystallized from water. After drying, one obtains the title compound as nearly colorless crystals (1.12 g) of mp. 138 C.
With hydrogenchloride; diisopropylamine; In tetrahydrofuran; 4B Preparation of <strong>[154471-65-5]1-methyl-3-trifluoromethylpyrazol</strong>-5-yl-boronic acid A solution of <strong>[154471-65-5]l-methyl-3-trifluoromethylpyrazol</strong> (2 g) in 10 ml THF is cooled under an inert gas atmosphere to -78 C. A 2 M solution of LDA (9.75 ml) is added dropwise. The mixture is stirred to 10 C for 1 h and cooled to -75 C. Trimethylborate (5.8 ml) is added and after stirring for 1 h at -75 C the mixture is stirred overnight at ambient temperature. The resulting reaction solution is added to 10 % hydrochloric acid (15 ml). The water phase is extracted 3 times with ethyl acetate and the combined organic phases are washed with water and a saturated sodium chloride solution. The organic phase is dried and evaporated and the residue is crystallized from water. After drying, one obtains the title compound as nearly colorless crystals (1.12 g) of mp. 138C.
  • 3
  • [ 13195-50-1 ]
  • [ 344591-91-9 ]
  • [ 1361380-64-4 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; at 110℃; for 0.5h;Inert atmosphere; Microwave irradiation; Examples 71-73Preparation of (2-fluorophenyl)-N-{5-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl](2-thienyl)}carboxamide (135) 1-Methyl-3-trifluoromethylpyrazole-5-boronic acid (97 mg, 0.5 mmol) and <strong>[13195-50-1]2-bromo-5-nitrothiophene</strong> (104 mg, 0.5 mmol) was dissolved in 2 mL dimethoxyethane and 2 mL EtOH. The 1 mL of 2 M Na2CO3 was added and the mixture was bubbled with Ar for 1 min before add tetrakis(triphenylphosphine)-palladium(0) (Pd(Ph3P)4, 60 mg, 0.05 mmol). The reaction was heated at 110° C. for 30 min under microwave initiator. The reaction mixture was worked-up with EtOAc extraction and product was purified by flash column and afforded 133 as yellow solid. Following hydrogenation under standard conditions, to a solution of 134 (37 mg, 0.15 mmol) in CH2Cl2 (10 mL) was added 2-fluorobenzoyl chloride, N,N-diisopropylethylamine (DIEA, 0.5 g, 0.7 mL, 4 mmol), and a catalytic amount of DMAP. The mixture was stirred for 2 h at room temperature. The reaction was quenched with saturated NaHCO3 (20 mL) and extracted with EtOAc (20 mL.x.2). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The residue was dissolved in THF (2 mL) and MeOH (2 mL). 1M NaOH (2 mL) was added and stirred for 0.5 h at room temperature. The reaction mixture was concentrated and worked-up with EtOAc-Brine. The crude product was purified by flash column and compound 135 (2.7 mg, 5percent) was obtained as yellow solid. LC-MS: calcd. for C16H11F4N3OS: 370 (M+1).
  • 4
  • [ 344591-91-9 ]
  • [ 3034-48-8 ]
  • [ 1361380-57-5 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; at 110℃; for 0.5h;Inert atmosphere; Microwave irradiation; Example 29Preparation of (2-chlorophenyl)-N-{2-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl](1,3-thiazol-5-yl)}carboxamide (67) Preparation of 2-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl]-5-nitro-1,3-thiazole (65): A mixture of <strong>[3034-48-8]<strong>[3034-48-8]2-bromo-5-nitrothiazol</strong>e</strong> (209 mg, 1 mmol), (1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)boronic acid (194 mg, 1 mmol), tetrakis(triphenylphosphine)-palladium(0) (Pd(Ph3P)4, 57 mg) and sodium carbonate (212 mg) in 3 ml DME, 0.5 ml EtOH and 0.5 ml water was heated under Ar in microwave reactor at 110° C. for 30 min. The reaction mixture was worked up with EA/brine. Org. phase was concentrated and then subjected to silica gel flash chromatography (0-30percent B; A: hexane; B: 50percent EA in hexane) to furnish 37.5 mg of 2-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl]-5-nitro-1,3-thiazole (65) as light yellow solid (yield: 13.5percent; purity>90percent).
 

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