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Chemical Structure| 785777-87-9 Chemical Structure| 785777-87-9

Structure of 785777-87-9

Chemical Structure| 785777-87-9

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Product Details of [ 785777-87-9 ]

CAS No. :785777-87-9
Formula : C5H2BrF3N2
M.W : 226.98
SMILES Code : BrC1=NC=CC(=N1)C(F)(F)F
MDL No. :MFCD09802248
InChI Key :RHCZXIKKGYOYQZ-UHFFFAOYSA-N
Pubchem ID :11436086

Safety of [ 785777-87-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 785777-87-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.2
Num. rotatable bonds 1
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 34.73
TPSA ?

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

25.78 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

2.15
Log Po/w (WLOGP)?

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

3.41
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.

1.49
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

2.65
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.3

Water Solubility

Log S (ESOL):?

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

-2.94
Solubility 0.261 mg/ml ; 0.00115 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.

-2.32
Solubility 1.08 mg/ml ; 0.00475 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

-3.4
Solubility 0.0908 mg/ml ; 0.0004 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.

-6.16 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

0.0
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)

1.83

Application In Synthesis of [ 785777-87-9 ]

* 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 [ 785777-87-9 ]

[ 785777-87-9 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 104048-92-2 ]
  • [ 785777-87-9 ]
  • 2
  • [ 186581-53-3 ]
  • [ 124-38-9 ]
  • [ 785777-87-9 ]
  • methyl 4-(trifluoromethyl)pyrimidine-2-carboxylate [ No CAS ]
  • 3
  • [ 785777-87-9 ]
  • 2,2'-dibromo-6,6'-bis(trifluoromethyl)-4,4'-bipyrimidyl [ No CAS ]
  • 4
  • [ 554457-27-1 ]
  • [ 785777-87-9 ]
  • [2-oxo-3-(4-trifluoromethyl-pyrimidin-2-yl)-2,3-dihydro-benzoimidazol-1-yl]-acetic acid <i>tert</i>-butyl ester [ No CAS ]
  • 5
  • [ 1332329-54-0 ]
  • [ 785777-87-9 ]
  • [ 1332329-55-1 ]
YieldReaction ConditionsOperation in experiment
29.8% With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane;Inert atmosphere; Reflux; A mixture of 4,5 Bis(diphenyl- phosphino)-9,9-dimethylxanthene[xanthopos](8.6 mg, 0.01488 mmol) and Tris(dibenzylideneacetone)di- palladium(0)[Pd2(dba)3](6.81 mg, 0.00744 mmol) in dry l ,4-dioxane(5 ml)was stirred vigorously and nitrogen was bubbled through the suspension for 30 minutes. 5-Bromo pyrimidine (19.7 mg, 0.1247 mmol), 3-(l ,4-Dioxa-8-aza- spiro[4.5]dec-8-yl)-4-methyl-phenylamine (30.96 mg, 0.1247 mmol) and dry cesium carbonate (100 mg,0.31 mmol) was added. Nitrogen was bubbled through for another 30 minutes; the mixture was allowed to reflux overnight. The mixture was cooled, diluted with ethylacetate, water was added and the layers were separated. The aqueous layer was extracted with ethyl acetate and the two organic extracts were combined. The organics were washed with brine, then dried (sodium sulfate), filtered and concentrated under vacuum. Further purification by silica gel chromatography using 5-10% ethyl acetate/hexane as eluent [3-(l ,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-4-methyl-phenyl]-(4- trifluoromethyl-pyrimidin-2-yl)-amine [30] as a pale yellow solid [Yield:4.05 mg, 29.8%]
  • 6
  • [ 40176-78-1 ]
  • [ 785777-87-9 ]
  • [ 1423778-66-8 ]
YieldReaction ConditionsOperation in experiment
12% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; at 85℃; for 3h;Inert atmosphere; General procedure: To a solution of 2-ethynylquinoline 9 (50 mg, 0.33 mmol) in triethylamine (0.4 mL) was added PdCl2(PPh3)2 (12 mg, 0.02 mmol), copper(I) iodide 98% (6 mg, 0.03 mmol) and 2- bromo-3-trifluoromethylpyridine (110 mg, 0.5 mmol). After the reaction was stirred at 85 C for 3 h, it was allowed to cool to room temperature and filtered through a pad of Celite by the aid of EtOAc. The filtrate was treated with water and extracted with EtOAc (3 x 10 mL). The organic layer was washed with water and brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. The crude oil was purified by column chromatography on silica gel (EtOAc/hexane = 1:1) to give 2-((3-(trifluoromethyl)pyridin-2-yl)ethynyl) quinoline 6a (48 mg, 49%)
  • 7
  • [ 785777-87-9 ]
  • [ 1333222-14-2 ]
  • 8
  • [ 67-56-1 ]
  • [ 201230-82-2 ]
  • [ 785777-87-9 ]
  • methyl 4-(trifluoromethyl)pyrimidine-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
41% With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; triethylamine; In acetonitrile; at 20 - 100℃;Inert atmosphere; [0607] Synthesis of methyl 4-(trifluoromethyl) pyrimidine-2-carboxylate: [0608] To a stirred solution of 2-bromo-4-(trifluoromethyl) pyrimidine (800 mg, 3.52 mmol) in MeOH: CH3CN (4: 1, 5 mL) under argon atmosphere was added Pd(dppf)2Cl2 (503 mg, 0.70 mmol), triethyl amine (1.0 mL, 7.04 mmol) at RT; heated to 100 C and stirred for 16 h under CO pressure. The reaction was monitored by TLC; after completion of the reaction, the volatiles were removed in vacuo to obtain the crude. The crude was purified through silica gel column chromatography using 25% EtOAc/ Hexanes to afford methyl 4-(trifluoromethyl) pyrimidine-2-carboxylate (300 mg, 41%) as Light pink solid. [0609] 1H-NMR (CDCI3, 500 MHz): delta 9.20 (d, 1H), 7.82 (d, 1H), 4.10 (s, 3H); LC-MS: 96.04%; 207 (M++l); (column; X-bridge C-18, (50 3.0 mm, 3.5 mu); RT 2.48 min. 0.05% TFA (aq.): ACN; 0.8 mL/min); TLC: 50% EtOAc/ Hexanes (R 0.3).
  • 9
  • [ 104048-92-2 ]
  • [ 785777-87-9 ]
YieldReaction ConditionsOperation in experiment
29% With N,N-dimethyl-aniline; phosphorus(V) oxybromide; In toluene; at 20 - 100℃;Inert atmosphere; [0604] Synthesis of 2-bromo-4-(trifluoromethyl) pyrimidine:[0605] To a stirred solution of 6-(trifluoromethyl)-l, 2-dihydropyrimidin-2-ol (2 g, 12.19 mmol) in toluene (40 mL) under argon atmosphere were added phosphorous oxybromide (5.24 g, 18.20 mmol), N, N-dimethyl aniline (156 mg, 1.20 mmol) at RT; heated to 100 C and stirred for 3 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with water (50 mL) and extracted with hexanes (2 x 50 mL). The combined organic extracts were washed with water (50 mL), dried over sodium sulphate, and concentrated in vacuo to obtain 2- bromo-4-(trifluoromethyl) pyrimidine (800 mg, 29%) as light yellow oil. [0606] 1H-NMR (CDCls, 500 MHz): delta 8.82 (d, 1H), 7.64 (d, 1H); TLC: 10% EtOAc/ Hexanes (R 0.8).
  • 10
  • (1SR,2SR,3SR)-methyl 1-fluoro-2-phenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxylate [ No CAS ]
  • [ 785777-87-9 ]
  • (1SR,2SR,3SR)-methyl 1-fluoro-2-phenyl-3-(4-(4-(trifluoromethyl)pyrimidin-2-yl)phenyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
230 mg With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; sodium carbonate; In 1,4-dioxane; water; at 100℃; for 17h; To a stirred solution of (1 S*,2S*,3S*)-methyl-2-(4-bromophenyl)-1 - f(1 S*,2S*,3S*)-Methyl-1-fluoro-2-phenyl-3-(4-(4-(trifluoromethyl)pyrimidin-2- yl)phenyl)cyclopropanecarboxylate luoro-3-phenylcyclopropane carboxylate (470 mg, 1 .47 mmol) in dioxane (1 0 mL) was added bis-pinacolato diboron (412 mg, 1 .62 mmol), Pd(dppf)CI2 (120 mg, 0.15mmol) and potassium acetate (720 mg, 7.35 mmol). The mixture was degassed with nitrogen and heated to 100 C for 2 h. The reaction mixture was diluted with H20 (20 ml_) and extracted into DCM (2 x 20 ml_). The organic phase was concentrated and the crude used in the next step. [00199] A solution of (1 S*,2S* 3S*)-methyl-1 -fluoro-2-phenyl-3-(4-(4 4 5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxylate (538 mg, 1 .47 mmol), Pd(dppf)2CI2 (169 mg, 0.1 5 mmol), <strong>[785777-87-9]2-bromo-4-(trifluoromethyl)pyrimidine</strong> (367 mg, 1 .62 mmol), and 2 M Na2C03 (aq) (2.2 ml_, 4.41 mmol) in dioxane (1 5 ml_) was stirred at 100 C for 17 h. The reaction mixture was diluted with water and extracted into DCM. The organic phase was passed through a phase separator and concentrated. Purification by flash silica column chromatography (gradient elution /'- hex to 30% EtOAc in /-hex) afforded the target compound (230 mg, 41 %). LCMS (ES+) 417 (M+H)+.
  • 11
  • [ 98-78-2 ]
  • [ 785777-87-9 ]
  • 3-(2-bromo-6-(trifluoromethyl)pyrimidin-4-yl)cyclopentanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% With ammonium peroxydisulfate; silver nitrate; In water; acetonitrile; at 60℃; for 2h; General procedure: Toa vial was added pyrimidine (0.42-0.65 mmol, 1.0 equiv.) (if solid), carboxylic acid (3.0 equiv.) (if solid), silver nitrate (4.0 equiv.) and ammonium persulfate (5.0equiv.). Acetonitrile (5 mL) and water(5 mL) were then added (followed by the pyrimidine and/or carboxylic acid if liquids) and the vial was capped and heated to 60 C for 2 h. The reaction mixture was monitored by TLC and LCMS. The reaction mixture was quenched by the addition of concentrated ammonium hydroxide (0.8 mL) and water (3.2 mL), diluted with brine and filtered through Celite. The filtrate was then extracted with DCM (3 x10 mL) and the organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was adsorbed onto silica and purified by flash chromatography (0-50% EtOAc in heptane) to afford the desired compound.
  • 12
  • [ 785777-87-9 ]
  • [ 1544496-24-3 ]
  • 13
  • [ 785777-87-9 ]
  • (1S*,2S*,3S*)-1-fluoro-N-hydroxy-2-phenyl-3-(4-(4-(trifluoromethyl)pyrimidin-2-yl)phenyl)cyclopropanecarboxamide [ No CAS ]
  • 14
  • [ 26687-82-1 ]
  • [ 785777-87-9 ]
  • C26H25F3N2O6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% Arctigenin (50mg, 0.134mmol) dissolved in 2ml of dry N,N-dimethylformamide (DMF) was added potassium carbonate (37mg, 0.268mmol) and stirred for 10min at room temperature. To this was added <strong>[785777-87-9]2-bromo-4-trifluoromethylpyrimidine</strong> (37mg, 0.161mmol) and was stirred at 120C for 8h. 10mL of ice water was added after cooling to room temperature and solids precipitated. It was filtered and the filter cake was washed with 5% potassium bisulfate solution. After recrystallization from methanol and dried in vacuo, it gave a 64mg white solid, yield 92%.
 

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