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Chemical Structure| 1544-85-0

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Product Details of [ 1544-85-0 ]

CAS No. :1544-85-0
Formula : C7H5F2NO2
M.W : 173.12
SMILES Code : NC1=CC2=C(OC(F)(F)O2)C=C1
MDL No. :MFCD00190144
InChI Key :CVYQRDKVWVBOFP-UHFFFAOYSA-N
Pubchem ID :2736893

Safety of [ 1544-85-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319-H412
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 1544-85-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 0
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 37.05
TPSA ?

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

44.48 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.63
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

1.82
Log Po/w (WLOGP)?

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

2.44
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.

0.88
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

1.58
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.67

Water Solubility

Log S (ESOL):?

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

-2.43
Solubility 0.643 mg/ml ; 0.00372 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.

-2.37
Solubility 0.732 mg/ml ; 0.00423 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

-2.33
Solubility 0.802 mg/ml ; 0.00463 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.

-6.06 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)

2.27

Application In Synthesis of [ 1544-85-0 ]

* 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 [ 1544-85-0 ]

[ 1544-85-0 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 1544-85-0 ]
  • [ 101537-64-8 ]
  • [ 877997-59-6 ]
YieldReaction ConditionsOperation in experiment
67% With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; N,N-dimethyl-formamide; at 60℃; for 16h; 3-[(Tert-butoxycarbonyl)amino]thiophene-2-carboxylic acid (7.3 g, 30.3 mmol) (step 2) was dissolved in DCM (155 niL), triethyl amine (12 mL), DMF (31 mL) and 2,2-difluoro- l,3-benzodioxol-5-amine (5 g, 29 mmol) was added. PyBOP (16.5 g, 32 mmol) was added and the mixture was stirred at 600C for 16 h. The reaction mixture was cooled and diluted with water and EtOAc. The organic layer was washed with water, dried with Na2SO4, and evaporated. The crude residue was purified using silica gel chromatography to yield the desired product (7.7 g, 67 %). 1H NMR (DMSO-J6) 69.95 (bs, IH), 7.95 (d, IH), 7.65, (s, IH), 7.45 (m, 2H), 7.10 (s, 2H), 1.50 (s, 9H); LCMS: 398.9 [M+H]+, RT 4.12 min.
  • 2
  • [ 1544-85-0 ]
  • [ 1171919-75-7 ]
  • tert-butyl (3R)-3-[(2-sulfanylacetyl)amino]piperidine-1-carboxylate [ No CAS ]
  • [ 530-62-1 ]
  • (R)-N-(1-(1H-imidazole-1-carbonyl)piperidin-3-yl)-5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
2.65% To a 40 mL microwave vial were added <strong>[1171919-75-7]2-chloro-4-iodonicotinonitrile</strong> (1.451 g, 5.488 mmol), bis(2-diphenylphosphinophenyl)ether (90 mg, 0.17 mmol), palladium(II) acetate (25 mg, 0.11 mmol), cesium carbonate (2.503 g, 7.683 mmol), 2,2-difluoro-5-aminobenzodioxole (1.0 g, in 1.0 mL dioxane), and dioxane (10 mL) and was purged with N2stream for 30 min. The reaction was heated in the microwave at 150 C for 30 min. To the reaction mixture was added fert-butyl (3R)-3-[(2-sulfanylacetyl)amino]piperi dine- 1-carboxy late (Intermediate 22) ( 8.44 mL, 5.49 mmol) and was purged with N2stream for 15 min. The reaction was heated in microwave at 150 C for 30 min. To the mixture was added CDI (3.6 g, 22 mmol) and was heated at 150 C for 30 min. The reaction mixture was extracted with EtOAc and the organic phase was washed with water and brine. The precipitate was filtered off through Celite. The organic phase was over anhydrous Na2SC>4, filtered, and concentrated to dryness. The reaction mixture was purified by flash column chromatography, then by HPLC to give the title compound as a brown solid (82.4 mg, 2.65% yield). MS (ESI): mass calcd. for C25Hi9F2N705S, 567.5; m/z found, 568.0 [M+H]+.1H NMR (500 MHz, CD3OD): δ 8.16 - 8.06 (m, 2H), 7.47 (s, 1H), 7.27 - 7.20 (m, 2H), 7.15 - 7.08 (m, 1H), 7.06 (s, 1H), 6.80 (d, J= 5.9 Hz, 1H), 5.16 - 5.06 (m, 1H), 4.17 (t, J = 12.0 Hz, 1H), 4.12 - 3.97 (m, 2H), 3.13 (t, J = 12.4 Hz, 1H), 2.86 - 2.71 (m, 1H), 1.92 (t, J= 13.3 Hz, 2H), 1.83 - 1.72 (m, 1H).
2.65% To a 40 mL microwave vial were added <strong>[1171919-75-7]2-chloro-4-iodonicotinonitrile</strong> (1.451 g, 5.488 mmol) , bis (2-diphenylphosphinophenyl) ether (90 mg, 0.17 mmol) , palladium (II) acetate (25 mg, 0.11 mmol) , cesium carbonate (2.503 g, 7.683 mmol) , 2, 2-difluoro-5-aminobenzodioxole (1.0 g, in 1.0 mL dioxane) , and dioxane (10 mL) and was purged with N2stream for 30 min. The reaction was heated in the microwave at 150 for 30 min. To the reaction mixture was added tert-butyl (3R) -3- [ (2-sulfanylacetyl) amino] piperidine-1-carboxylate (Intermediate 22) (8.44 mL, 5.49 mmol) and was purged with N2stream for 15 min. The reaction was heated in microwave at 150 for 30 min. To the mixture was added CDI (3.6 g, 22 mmol) and was heated at 150 for 30 min. The reaction mixture was extracted with EtOAc and the organic phase was washed with water and brine. The precipitate was filtered off through Celite. The organic phase was over anhydrous Na2SO4, filtered, and concentrated to dryness. The reaction mixture was purified by flash column chromatography, then by HPLC to give the title compound as a brown solid (82.4 mg, 2.65yield) . MS (ESI) : mass calcd. for C25H19F2N7O5S, 567.5 m/z found, 568.0 [M+H]+.1H NMR (500 MHz, CD3OD) : δ 8.16 -8.06 (m, 2H) , 7.47 (s, 1H) , 7.27 -7.20 (m, 2H) , 7.15 -7.08 (m, 1H) , 7.06 (s, 1H) , 6.80 (d, J 5.9 Hz, 1H) , 5.16 -5.06 (m, 1H) , 4.17 (t, J 12.0 Hz, 1H) , 4.12 -3.97 (m, 2H) , 3.13 (t, J 12.4 Hz, 1H) , 2.86 -2.71 (m, 1H) , 1.92 (t, J 13.3 Hz, 2H) , 1.83 -1.72 (m, 1H) .
  • 3
  • [ 1544-85-0 ]
  • [ 1171919-75-7 ]
  • tert-butyl (3R)-3-[(2-sulfanylacetyl)amino]piperidine-1-carboxylate [ No CAS ]
  • (R)-tert-butyl 3-(3-amino-4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)amino)thieno[2,3-b]pyridine-2-carboxamido)piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
80.43% To a Biotage vial were added 2-chloro-4- iodonicotinonitrile (1.03 g, 3.90 mmol), 2,2-difluoro-5-aminobenzodioxole (710 mg, 3.90 mmol), bis(2-diphenylphosphinophenyl)ether (64 mg, 0.12 mmol), palladium(II) acetate (17 mg, 0.078 mmol), CS2CO3(1.777 g, 5.453 mmol), and dioxane (7.8 mL) and was stirred at rt while purging with N2stream for 30 min, then it was placed in heating block at 110 C for 1.5 h. Next, fert-butyl (3R)-3-[(2-sulfanylacetyl)amino]piperidine-1-carboxylate (Intermediate 22) (6.0 mL, 3.9 mmol) was added and it was purged with N2for 15 min, then was heated at 90 C for 1.5 hr. The reaction mixture was diluted with EtOAc, filtered through Celite, concentrated to dryness, and purified by flash column chromatography to give the title compound as a yellow oil (1.715 g, 80.43% yield).
 

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