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Chemical Structure| 311-86-4 Chemical Structure| 311-86-4

Structure of 311-86-4

Chemical Structure| 311-86-4

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Product Details of [ 311-86-4 ]

CAS No. :311-86-4
Formula : C3H4BrF3O
M.W : 192.96
SMILES Code : OCC(Br)C(F)(F)F
MDL No. :MFCD09763638
InChI Key :FJNZCBUVTKMTNI-UHFFFAOYSA-N
Pubchem ID :534005

Safety of [ 311-86-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H315-H319-H335
Precautionary Statements:P210-P261-P305+P351+P338
Class:3
UN#:1993
Packing Group:

Computational Chemistry of [ 311-86-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 25.76
TPSA ?

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

20.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.29
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

1.48
Log Po/w (WLOGP)?

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

2.57
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.

1.53
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

1.75
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.72

Water Solubility

Log S (ESOL):?

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

-1.84
Solubility 2.81 mg/ml ; 0.0146 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.

-1.51
Solubility 5.94 mg/ml ; 0.0308 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

-1.5
Solubility 6.1 mg/ml ; 0.0316 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.

-6.43 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

3.0
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)

2.1

Application In Synthesis of [ 311-86-4 ]

* 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 [ 311-86-4 ]

[ 311-86-4 ] Synthesis Path-Downstream   1~15

  • 1
  • [ 677-21-4 ]
  • [ 311-86-4 ]
YieldReaction ConditionsOperation in experiment
90.2% 4.0mol of glacial acetic acid was added to the reaction flask, and the temperature was increased to 90 C with stirring. 0.4mol of NBS and 6.4g of concentrated sulfuric acid were added, and 3,3,3-trifluoropropene was introduced at the same time. After the reaction system was clarified, 0.20mol of NBS and 3.2 G of concentrated sulfuric acid, the reaction system clarified, then add 0.40molNBS and 6.4g concentrated sulfuric acid, the reaction system clarified, 80C reaction 2h, temperature to 100C to continue the reaction 2h, 3,3,3-trifluoropropene into the 1.3mol . Cooling to 40 C, adding 7mol methanol stirring under reflux, the reaction 9h. Methanol and methyl acetate were distilled off at normal pressure. After cooling, the solid was filtered off, and 2-bromo-3,3,3-trifluoropropanol was obtained by distillation under reduced pressure. The yield was 90.2% and the content was 99.1%.
  • 4
  • [ 383-68-6 ]
  • [ 311-86-4 ]
  • [ 64-19-7 ]
YieldReaction ConditionsOperation in experiment
89% With sulfuric acid; water; for 4h;Heating / reflux; EXAMPLE 2 In accordance with example 2, 1 L of water is placed in a 2 L single-necked round-bottomed flask fitted with a condenser. Concentrated H2SO4 (100 ml) is added slowly to the flask to produce a reaction mixture. Acetyl bromohydrin (180 g) is then added and the mixture is heated to reflux. The mixture is refluxed for 3 hrs until the mixture becomes homogeneous and further refluxed for 1 hour and then cooled to room temperature. The reaction mixture is saturated with NaCl and extracted with ether (200 ml*5). Combined ether layers are washed with saturated NaHCO3, dried over anhydrous Na2SO4 and evaporated to yield bromohydrin 131 g. Yield=131 g. (89%) 1H NMR (CDCl3, 300 MHz) delta ppm: 3.90-4.02 (m, 1H), 4.04-4.14 (m, 1H), 4.22-4.34 (m, 1H).
  • 5
  • [ 311-86-4 ]
  • [ 75-56-9 ]
YieldReaction ConditionsOperation in experiment
69% With sodium hydroxide; In water; at 85℃; EXAMPLE 3; Bromohydrin 65 g. Aq. NaOH (20%) 100 g. In accordance with example 3, 65 g. bromohydrin is taken in a 300 ml three-necked round-bottomed flask fitted with a septum, a thermometer jacket, and a distillation set up. The bromohydrin is stirred and heated to 85 C. (oil bath temperature was 95 C.). NaOH (20% solution, 100 g) is introduced through septum by syringe. Product distills as NaOH is introduced. Yield=26 g. (69%) 1H NMR: (CDCl3, 300 MHz) delta ppm: 2.90-2.94(m, 1H), 2.96-3.02(m, 1H), 3.38-3.46(m, 1H).
  • 6
  • [ 383-68-6 ]
  • [ 311-86-4 ]
YieldReaction ConditionsOperation in experiment
90.8% With sulfuric acid; In methanol; for 4h;Reflux; Methanol: 64.1 g,3,3,3-trifluoro-2-bromopropyl acetate: 235 g,Concentrated sulfuric acid: 4.7g,Was added to a 0.5 L reaction flask,Stirring and heating to reflux,Reflux 4.0h,Most of the methanol and by-product methyl acetate were distilled off at atmospheric pressure,And distilled to give 175.2 g of a colorless liquid in a yield of 90.8%.
With sulfuric acid; In methanol; at 70℃; for 4h; Using an excess of trifluoropropene into a mixture of 8000 mg of 20% fuming sulfuric acid and 1600 mg of bromine,Keep the temperature at 12-22 C until the red and brown of the bromine in the flask disappears and stop venting.15 ml of acetic acid was added to the mixed solution, and heating was continued at 95 C for 1 h. The product was subjected to extraction and washing to give 2-bromo-3,3,3-trifluoroacetate. After color-mass spectrometry analysis,The yield was 76.14% and the selectivity was 95%.Add to 1790 mg of 2-bromo-3,3,3-trifluoroacetate35.8 mg of concentrated sulfuric acid and 488 mg of methanol were refluxed in an oil bath at 70 C for 4 h.Excess methanol and ethyl formate were distilled off from the product to give 2-bromo-3,3,3-trifluoro-1-propanol.After chromatographic analysis, the yield was 92.58%, as shown in Figure 3.
  • 7
  • [ 311-86-4 ]
  • [ 359-41-1 ]
YieldReaction ConditionsOperation in experiment
80.3% With calcium hydroxide; In water; at 38 - 40℃; for 1h; Calcium hydroxide: 72.8 gAnd 332 g of water were added to a reaction flask equipped with a rectification apparatus,Heated to 90 C with stirring,163.8 g of <strong>[311-86-4]3,3,3-trifluoro-2-bromopropanol</strong> was added dropwise,Control the distillation head temperature of 38-40 ,After the addition of the reaction for 1.0 h,The yield of trifluoropropylene oxide was 80.3%.
74% With calcium hydroxide; In water; at 90℃; for 1h; 733.2 mg of calcium hydroxide and 3343.3 mg of water were added to the reaction flask with the rectification apparatus.The mixture was heated to 90 C with stirring, and 1345 mg of <strong>[311-86-4]2-bromo-3,3,3-trifluoro-1-propanol</strong> was slowly added dropwise thereto for 1 h to obtain 1,1,1-trifluoro-2,3-epoxypropane. After chromatographic analysis, the yield was 74% and the selectivity was 100%, as shown in Figure 4.
  • 8
  • [ 311-86-4 ]
  • [ 358-23-6 ]
  • [ 1330062-60-6 ]
  • 9
  • [ 311-86-4 ]
  • 1-[1-(3-azetidin-3-yl-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine dihydrochloride [ No CAS ]
  • 2-(3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}azetidin-1-yl)-3,3,3-trifluoropropan-1-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
30% With triethylamine; In N,N-dimethyl-formamide; acetonitrile; at 70℃; Example 113 2-(3-{3-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}azetidin-1-yl)-3,3,3-trifluoropropan-1-ol To a mixture of 1-[1-(3-azetidin-3-yl-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine dihydrochloride (20 mg, 0.04 mmol, chrial intermediate from peak 1 of Example 1, step 7) and triethylamine (19 muL, 0.13 mmol) in acetonitrile (0.6 mL) was added <strong>[311-86-4]2-bromo-3,3,3-trifluoropropan-1-ol</strong> (from Synquest Labs, 9.2 mg, 0.048 mmol). N,N-dimethylformamide (0.3 mL) was added, which created a clear solution that was stirred at 70 C. overnight. The mixture was diluted water and purified using RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give 6.6 mg (30%) of the desired product. The product was isolated as a mixture of diastereomers. LCMS calculated for C22H27ClF3N6O2 (M+H)+: m/z=499.2. Found: 499.1.
  • 10
  • [ 311-86-4 ]
  • 1-[1-(3-azetidin-3-yl-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine dihydrochloride [ No CAS ]
  • 2-(3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}azetidin-1-yl)-3,3,3-trifluoropropan-1-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
30% With triethylamine; In N,N-dimethyl-formamide; acetonitrile; at 70℃; To a mixture of 1-[1-(3-azetidin-3-yl-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine dihydrochloride (20 mg, 0.04 mmol, chiral intermediate from peak 1 of Example 1, step 7) and triethylamine (19 muL, 0.13 mmol) in acetonitrile (0.6 mL) was added <strong>[311-86-4]2-bromo-3,3,3-trifluoropropan-1-ol</strong> (from Synquest Labs, 9.2 mg, 0.048 mmol). N,N-dimethylformamide (0.3 mL) was added, which created a clear solution that was stirred at 70 C. overnight. The mixture was diluted water and purified using RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give 6.6 mg (30%) of the desired product. The product was isolated as a mixture of diastereomers. LCMS calculated for C22H27ClF3N6O2 (M+H)+: m/z=499.2; Found: 499.1.
  • 11
  • [ 311-86-4 ]
  • [ 32315-10-9 ]
  • [ 1354041-25-0 ]
  • 2-bromo-3,3,3-trifluoropropyl(2-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)pyrimidin-4-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
4% To a cold mixture of triphosgene (0.9 equiv.) and <strong>[311-86-4]2-bromo-3,3,3-trifluoropropan-1-ol</strong> (2equiv.) in THF was added pyridine (2 equiv.). The mixture was stirred at 0 C for 30 mm. In a separate flask, a suspension of Intermediate 2 (1 equiv.) in pyridine (2 equiv.) was cooled to 0C. To this suspension was added the mixture of triphosgene and bromopropanol via syringe, and the resulting mixture was heated to 60 C for 24 h. Contents were concentrated in vacuo, and the residue was diluted with ethyl acetate and washed with iN HC1 solution. The organic layer was dried over Mg504, filtered, and concentrated in vacuo to give a crude oil. The oil was purified via silica gel chromatography utilizing a 0-100% ethyl acetate/hexanes gradient todeliver the desired carbamate intermediate, 2-bromo-3,3,3-trifluoropropyl(2-( 1 -(2-fluorobenzyl)-5 -(isoxazol-3 -yl)- 1 H-pyrazol-3 -yl)pyrimidin-4-yl) carbamate (77 mg, 4% yield) as a light brown oil.1H NMR (500 MHz, CDC13) oe ppm 8.46 - 8.48 (m, 1 H), 8.07 (br. s., 1 H), 7.86 (d, 1 H), 7.44 -7.47 (m, 1 H), 7.17 - 7.24 (m, 1 H), 7.00 - 7.07 (m, 1 H), 6.93 - 7.00 (m, 1 H), 6.78 - 6.85 (m, 1 H), 6.57 - 6.62 (m, 1 H), 6.02 (s, 2 H), 4.28 (quind, 1 H), 3.93 - 4.15 (m, 2 H).
  • 12
  • [ 311-86-4 ]
  • [ 2240-88-2 ]
YieldReaction ConditionsOperation in experiment
95% With hydrogen; potassium carbonate; In methanol; at 80℃; under 37503.8 Torr; for 3h;Autoclave; 54 g of <strong>[311-86-4]2-bromo-3,3,3-trifluoropropanol</strong>, 79 g of methanol, 9.7 g of activated RaneyNi catalyst and 19.3 g of potassium carbonate were charged into a 300 mL autoclave, stirred, evacuated and replaced with hydrogen After three times, pressure 5Mpa, heated to 80 C, the reaction 3.0h, stop the reaction, cooling, discharge, distillation to 3,3,3 - trifluoropropanol; Yield 95.0%.
  • 13
  • [ 311-86-4 ]
  • [ 4270-70-6 ]
  • C18H15S(1+)*C3H4F3O4S(1-) [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% Synthesis of Compound (m-2) (0347) To a 200 mL eggplant shaped flask were charged 5.0 g (26 mmol) of <strong>[311-86-4]2-bromo-3,3,3-trifluoropropan-1-ol</strong> (the compound (m-1)), 6.5 g (52 mmol) of Na2SO4 and 40 mL of H2O, and the mixture was stirred at 85 C. for 48 hours under a nitrogen atmosphere. After cooling to room temperature, 7.5 g (25 mmol) of triphenylsulfonium chloride and 120 mL of dichloromethane were added to the reaction solution, and the mixture was stirred at room temperature for 3 hours. After completing the reaction, only the organic layer was recovered, and the recovered organic layer was washed three times with 20 mL of water and dried over anhydrous magnesium sulfate. Thereafter, the residue obtained by concentrating the organic layer in vacuo was purified by silica gel column chromatography (developing solvent: dichloromethane/MeOH=10/1 (volume ratio)) to obtain 6.2 g of a compound (m-2) (yield 52%).
  • 14
  • [ 359-41-1 ]
  • [ 311-86-4 ]
  • [ 124-38-9 ]
  • [ 167951-80-6 ]
  • [ 431-39-0 ]
YieldReaction ConditionsOperation in experiment
With 1H-imidazole; 1,2-dibromohexafluoropropane; water; at 50 - 120℃; under 15001.5 Torr; for 28h;Autoclave; Adding a moisture content of 4000 ppm in a 50 mL stainless steel autoclave equipped with agitation3,3,3-trifluoropropylene oxide (33.6 g, 0.3 mol), 3-bromo-1,1,1-trifluoro-2-propanol (2.3 g, 12 mol),2,3-dibromo-1,1,1,2,3,3-hexafluoropropane (5.6 g, 18 mol), imidazole (1.6 g, 24 mmol),After sealing, the reactor was replaced twice with CO2, and the stirring was set to a reaction temperature of 120 C.Continuously pass CO2 to maintain the reaction pressure at 2MPa, react for 4h, cool to normal temperature, and slowly releaseTo the excess CO2 gas, 50% water of a molar amount of 3,3,3-trifluoroepoxypropane was added to the reaction solution, and the reaction was stirred at 50 C for about 24 hours to obtain 3,3,3-trifluoro. Crude product of propylene carbonate and 3,3,3-trifluoro-1,2-propanediol, analysis of reaction product distribution by gas chromatography, separation,Refined process to get the target product3,3,3-trifluoropropene carbonate and42.3 g of 3,3,3-trifluoro-1,2-propanediol was used to calculate the yield
  • 15
  • [ 311-86-4 ]
  • [ 359-41-1 ]
  • [ 1514-82-5 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In water; at 0 - 95℃; 2-bromo-1 ,1 , 1-trifluoropropan-3-ol (10 g, 0.0524mol) was placed in a 2-necked round bottom flask fitted with a distillation set up and then heated to 95 C. Sodium hydroxide (3 g, 0.0754 mol) was dissolved in water (12 g) at 0 C with stirring. Once the solution was homogenous it was then added dropwise to the 2-bromo-1 ,1 , 1-trifluoropropan-3-ol with rapid stirring via dropping funnel. As the head temperature reached 60 C clear liquid was collected in a receiver flask (4.2 g). GC area%: 1 , 1 , 1-trifluoro-1 ,2- epoxypropane (52%), 2-bromo-3,3,3-trifluoropropene + ethyl ether (26%), 3-acetoxy-2- bromo-1 , 1 , 1-trifluoropropane (7%), acetone (2%), unknown (13%).
 

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