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Structure of 127733-40-8

Chemical Structure| 127733-40-8

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Product Details of [ 127733-40-8 ]

CAS No. :127733-40-8
Formula : C10H9F6N
M.W : 257.18
SMILES Code : C[C@H](N)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1
MDL No. :MFCD03093013
InChI Key :PFVWEAYXWZFSSK-YFKPBYRVSA-N
Pubchem ID :1512509

Safety of [ 127733-40-8 ]

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

Computational Chemistry of [ 127733-40-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 6
Fraction Csp3 0.4
Num. rotatable bonds 3
Num. H-bond acceptors 7.0
Num. H-bond donors 1.0
Molar Refractivity 48.93
TPSA ?

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

26.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.35
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

2.95
Log Po/w (WLOGP)?

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

5.72
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.

3.87
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

3.74
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.73

Water Solubility

Log S (ESOL):?

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

-3.36
Solubility 0.113 mg/ml ; 0.00044 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.

-3.16
Solubility 0.178 mg/ml ; 0.000694 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

-4.25
Solubility 0.0144 mg/ml ; 0.0000561 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

Yes
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.

-5.77 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

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<0.0
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)

2.05

Application In Synthesis of [ 127733-40-8 ]

* 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 [ 127733-40-8 ]

[ 127733-40-8 ] Synthesis Path-Downstream   1~32

  • 1
  • [ 127733-38-4 ]
  • N-[1-(3,5-Bis-trifluoromethyl-phenyl)-ethyl]-O-methyl-hydroxylamine [ No CAS ]
  • [ 127733-40-8 ]
  • [ 127733-47-5 ]
  • 2
  • [ 384824-41-3 ]
  • [ 127733-40-8 ]
YieldReaction ConditionsOperation in experiment
5%-palladium/activated carbon; In methanol; at 60℃; under 1500.15 Torr; for 22.0h;Heating; 13.3 g (24.95 mmol, 1 eq) of the p-toluenesulfonate of optically active secondary amine (4a) purified with reference to Example 36 (4a.p-toluenesulfonate, 99.6% de, major form: S-S form) and 100 ml (50 mmol, 2 eq) of 0.5 N aqueous NaOH were added to 50 ml of toluene, followed by stirring for 30 minutes at room temperature, separating statically, extracting the recovered aqueous layer with toluene, washing the combined recovered organic layers with saturated brine, drying with an hydrous sodium sulfate, filtering, concentrating and vacuum drying to obtain an optically active secondary amine (4a) having the structure indicated below at the quantitative yield. [C00047] [00196] The resulting 4a was dissolved in 26 ml of methanol, followed by the addition of 0.45 g (0.125 wt %) of 5% palladium/active carbon (water content: 50 wt %), setting the hydrogen pressure to 0.2 MPa and stirring for 22 hours at 60 C. Following completion of the reaction, the reaction liquid was filtered with Celite, concentrated and vacuum dried to obtain a crude product of optically active 1-(3, 5-bis-trifluoromethylphenyl)ethylamine (5a) having the structure indicated below at the quantitative yield. The crude product was purified by simple distillation (96-97 C./31 mmHg) to obtain 5.41 g of a highly pure product (total yield for the two steps: 84%). GC purity and ee were 99.4% and 99.4% ee, respectively.
  • 3
  • [ 127733-40-8 ]
  • [ 742097-64-9 ]
  • Thiazole-4-carboxylic acid (4-{3-[(S)-1-(3,5-bis-trifluoromethyl-phenyl)-ethyl]-thioureido}-phenyl)-amide [ No CAS ]
  • 4
  • [ 127733-40-8 ]
  • [ 742097-66-1 ]
  • [1,2,3]Thiadiazole-4-carboxylic acid (4-{3-[(S)-1-(3,5-bis-trifluoromethyl-phenyl)-ethyl]-thioureido}-phenyl)-amide [ No CAS ]
  • 5
  • [ 127733-40-8 ]
  • [ 742097-78-5 ]
  • N-(5-[({(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}amino)carbothioyl]amino}-2-pyridinyl)-1,2,3-thiadiazole-4-carboxamide [ No CAS ]
  • 6
  • [ 127733-40-8 ]
  • [ 273384-73-9 ]
  • N-(5-[({(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}amino)carbothioyl]amino}-2-pyridinyl)-1,3-thiazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
In acetonitrile; EXAMPLE 91(.) N-(5-[({(1 S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}amino)carbothioyl]amino}-2-pyridinyl)-1,3-thiazole-4-carboxamide A mixture of N-(5-isothiocyanato-2-pyridinyl)-1,3-thiazole-4-carboxamide (0.36 g) and (S)-alpha-methyl-3,5-bis(trifluoromethyl)-benzenemethanamine (0.36 g) is heated with acetonitrile (10 mL) until all solids are dissolved. The solution is allowed to stand for 12 hours. A white solid forms and is collected by filtration (0.40 g). [M+H] 520.
  • 9
  • [ 672906-98-8 ]
  • [ 127733-40-8 ]
  • 10
  • [ 127733-40-8 ]
  • [ 127733-47-5 ]
  • [ 104-15-4 ]
  • [ 384824-36-6 ]
  • C7H8O3S*C10H9F6N [ No CAS ]
YieldReaction ConditionsOperation in experiment
In hexane; toluene; at 20 - 70℃; for 24.5h; 1.02 g (3.97 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=7.4:1) and 0.68 g (3.59 mmol, 0.9 eq) of p-toluenesulfonic acid monohydrate were added to 6.5 ml of toluene, followed by stirring for 30 minutes at 60-70 C., the addition of 6 ml of n-hexane and allowing to cool to room temperature and stand for one day. The precipitated crystals were filtered, washed with a small amount of n-hexane and vacuum dried to obtain 0.20 g of crystals having the structure represented by the formula below and 1.44 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 82.7% ee (major form is the S form) and 74.2% ee (major form is the S form). [C00039] [00180] 1H-NMR (TMS, DMSO): 1.54 (d, 6.8 Hz, 3H), 2.28 (s, 3H), 4.69 (q, 6.8 Hz, 1H), 7.10 (d, 8.3 Hz, 2H), 7.46 (d, 8.3 Hz, 2H), 8.17 (s, 1H), 8.23 (s, 2H), 8.30 (br, 31).
  • 11
  • [ 147-71-7 ]
  • [ 127733-40-8 ]
  • [ 127733-47-5 ]
  • [ 384824-37-7 ]
  • C4H6O6*C10H9F6N [ No CAS ]
YieldReaction ConditionsOperation in experiment
In methanol; for 12.5h;Heating / reflux; 0.94 g (3.64 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=7.4:1) and 0.55 g (3.64 mmol, 1 eq) of d-tartaric acid were added to 30 ml of methanol, followed by stirring for 30 minutes under reflux, allowing to cool to room temperature and stand for one half day. The precipitated crystals were filtered, washed with a small amount of methanol and vacuum dried to obtain 1.01 g of crystals having the structure represented by the formula below and 0.48 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 91.4% ee (major form is the S form) and 43.8% ee (major form is the S form). [C00040] [00182] 1H-NMR (TMS, DMSO): 1.45 (d, 6.8 Hz, 3H), 3.92 (s, 2H), 4.52 (q, 6.8 Hz, 1H), 6408 (s, 1H), 8.19 (s, 2H).
  • 12
  • [ 17199-29-0 ]
  • [ 127733-40-8 ]
  • [ 127733-47-5 ]
  • [ 384824-39-9 ]
  • C8H8O3*C10H9F6N [ No CAS ]
YieldReaction ConditionsOperation in experiment
In hexane; toluene; for 48.5h;Heating / reflux; 0.64 g (2.49 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=3.8:1) and 0.17 g (1.12 mmol, 0.45 eq) of (S)-mandelic acid were added to 3 ml of toluene, followed by stirring for 30 minutes under reflux, the addition of 1.5 ml of n-hexane and allowing to cool to room temperature and stand for 2 days in a refrigerator. The precipitated crystals were filtered, washed with a small amount of n-hexane and vacuum dried to obtain 0.53 g of crystals having the structure represented by the formula below and 0.28 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 96.1% ee (major form is the S form) and 4.7% ee (major form is the S form). [C00041] [00184] 1H-NMR (TMS, DMSO): 1.39 (d, 6.8 Hz, 3H), 4.41 (q, 6.5 Hz, 1H), 4.71 (d, 2.0 Hz, 1H), 7.19 (t, 7.3 Hz, 1H), 7.26 (t, 7.3 Hz, 2H), 7.36 (d, 7.3 Hz, 2H), 8.01 (s, 1H), 8.15 (s, 2H).Example 33Recrystallization Purification by (s)-Mandelic Acid Salt of Optically Active 1-(3.5-Bis-trifluoromethylphenyl)ethylamine (5a) [00185] 0.80 g (3.10 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=8.8:1) and 0.47 g (3.09 mmol, 1 eq) of (S)-mandelic acid were added to 4.5 ml of toluene, followed by stirring for 30 minutes under reflux, the addition of 1.8 ml of n-hexane, allowing to cool to room temperature, adding seed crystals and allowing to stand for 3 hours. The precipitated crystals were filtered, washed with a small amount of a-hexane and vacuum dried to obtain 0.89 g of crystals having the structure represented by the formula below and 0.35 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 90.7% ee (major form is the S form) and 58.1% ee (major form is the S form). [C00042] [00186] The 1H-NMR spectrum was the same as that of Example 32.
In toluene; at 20 - 80℃; for 1.5h;Heating; 0.89 g of (S)-mandelic acid salt of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a) (5a (S)-mandelate, enantiomer ratio/S form:R form=95.5:4.5) were added to 10 ml of toluene, followed by stirring for 30 minutes at 80 C. and allowing to cool to room temperature and stand for 1 hour. The precipitated crystals were filtered, washed with a small amount of toluene and vacuum dried to obtain 0.71 g of crystals having the structure represented by the formula below and 0.18 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 99.7% ee (major form is the S form) and 82.7% ee (major form is the S form). [C00043] [00188] The 1H-NMR spectrum was the same as that of Example 32.
  • 13
  • [ 384824-41-3 ]
  • [ 511256-29-4 ]
  • [ 127733-40-8 ]
  • [ 127733-47-5 ]
YieldReaction ConditionsOperation in experiment
75% With hydrogen;5%-palladium/activated carbon; In ethanol; at 55℃; under 1500.15 Torr; for 12.0h; [00108] 181 mg (0.5 mmol) of the crude product of optically active secondary amine (4a) produced in Example 7 and 18 mg (0.25 wt %) of 5% palladium/active carbon (water content: 50 wt %) were added to 2 ml of ethanol followed by setting the hydrogen pressure to 0.2 MPa and stirring for 12 hours at 55 C. Following completion of the reaction, the reaction liquid was filtered with Celite, concentrated and vacuum dried to obtain 96 mg of a crude product of the optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a) represented by the following formula: [C00016] [00109] The yield was 75%. Conversion, selectivity at the cleavage position (the previously mentioned a:b) and optical purity of the crude product were determined by chiral GC, and found to be 99%, a:b=1:99 and 76% ee, respectively.
  • 14
  • [ 384824-36-6 ]
  • C7H8O3S*C10H9F6N [ No CAS ]
  • [ 127733-40-8 ]
  • [ 127733-47-5 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In water; 1.02 g (3.97 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=7.4:1) and 0.68 g (3.59 mmol, 0.9 eq) of p-toluenesulfonic acid monohydrate were added to 6.5 ml of toluene, followed by stirring for 30 minutes at 60-70 C., the addition of 6 ml of n-hexane and allowing to cool to room temperature and stand for one day. The precipitated crystals were filtered, washed with a small amount of n-hexane and vacuum dried to obtain 0.20 g of crystals having the structure represented by the formula below and 1.44 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 82.7% ee (major form is the S form) and 74.2% ee (major form is the S form). [C00039] [00180] 1H-NMR (TMS, DMSO): 1.54 (d, 6.8 Hz, 3H), 2.28 (s, 3H), 4.69 (q, 6.8 Hz, 1H), 7.10 (d, 8.3 Hz, 2H), 7.46 (d, 8.3 Hz, 2H), 8.17 (s, 1H), 8.23 (s, 2H), 8.30 (br, 31).
  • 15
  • [ 384824-37-7 ]
  • C4H6O6*C10H9F6N [ No CAS ]
  • [ 127733-40-8 ]
  • [ 127733-47-5 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In water; 0.94 g (3.64 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=7.4:1) and 0.55 g (3.64 mmol, 1 eq) of d-tartaric acid were added to 30 ml of methanol, followed by stirring for 30 minutes under reflux, allowing to cool to room temperature and stand for one half day. The precipitated crystals were filtered, washed with a small amount of methanol and vacuum dried to obtain 1.01 g of crystals having the structure represented by the formula below and 0.48 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 91.4% ee (major form is the S form) and 43.8% ee (major form is the S form). [C00040] [00182] 1H-NMR (TMS, DMSO): 1.45 (d, 6.8 Hz, 3H), 3.92 (s, 2H), 4.52 (q, 6.8 Hz, 1H), 6408 (s, 1H), 8.19 (s, 2H).
  • 16
  • [ 384824-39-9 ]
  • C8H8O3*C10H9F6N [ No CAS ]
  • [ 127733-40-8 ]
  • [ 127733-47-5 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In water; 0.64 g (2.49 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=3.8:1) and 0.17 g (1.12 mmol, 0.45 eq) of (S)-mandelic acid were added to 3 ml of toluene, followed by stirring for 30 minutes under reflux, the addition of 1.5 ml of n-hexane and allowing to cool to room temperature and stand for 2 days in a refrigerator. The precipitated crystals were filtered, washed with a small amount of n-hexane and vacuum dried to obtain 0.53 g of crystals having the structure represented by the formula below and 0.28 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 96.1% ee (major form is the S form) and 4.7% ee (major form is the S form). [C00041] [00184] 1H-NMR (TMS, DMSO): 1.39 (d, 6.8 Hz, 3H), 4.41 (q, 6.5 Hz, 1H), 4.71 (d, 2.0 Hz, 1H), 7.19 (t, 7.3 Hz, 1H), 7.26 (t, 7.3 Hz, 2H), 7.36 (d, 7.3 Hz, 2H), 8.01 (s, 1H), 8.15 (s, 2H).Example 33Recrystallization Purification by (s)-Mandelic Acid Salt of Optically Active 1-(3.5-Bis-trifluoromethylphenyl)ethylamine (5a) [00185] 0.80 g (3.10 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=8.8:1) and 0.47 g (3.09 mmol, 1 eq) of (S)-mandelic acid were added to 4.5 ml of toluene, followed by stirring for 30 minutes under reflux, the addition of 1.8 ml of n-hexane, allowing to cool to room temperature, adding seed crystals and allowing to stand for 3 hours. The precipitated crystals were filtered, washed with a small amount of a-hexane and vacuum dried to obtain 0.89 g of crystals having the structure represented by the formula below and 0.35 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 90.7% ee (major form is the S form) and 58.1% ee (major form is the S form). [C00042] [00186] The 1H-NMR spectrum was the same as that of Example 32.Example 34Recrystallization Purification by (S)-Mandelic Acid Salt of Optically Active 1-(3,5-Bis-trifluoromethylphenyl)ethylamine (5a) [00187] 0.89 g of (S)-mandelic acid salt of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a) (5a (S)-mandelate, enantiomer ratio/S form:R form=95.5:4.5) were added to 10 ml of toluene, followed by stirring for 30 minutes at 80 C. and allowing to cool to room temperature and stand for 1 hour. The precipitated crystals were filtered, washed with a small amount of toluene and vacuum dried to obtain 0.71 g of crystals having the structure represented by the formula below and 0.18 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 99.7% ee (major form is the S form) and 82.7% ee (major form is the S form). [C00043] [00188] The 1H-NMR spectrum was the same as that of Example 32.
  • 17
  • [ 187085-97-8 ]
  • [ 127733-40-8 ]
  • [ 127733-47-5 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 101; (1alpha)-N-[(1alpha')-1-(3,5-Bis(trifluoromethyl)phenyl)ethyl]-1-(1-piperazinyl)indancarboxamide dihydrochloride; Step A; (1alpha')-1-[3,5-Bis(trifluoromethyl)phenyl]ethylamine; (1RS)-1-[3,5-Bis(trifluoromethyl)phenyl]ethylamine is converted into a salt using (L)-tartaric acid, the mixture of diastereoisomers thereby obtained is separated and then reconversion to the base is carried out on each of the two diastereoisomers. The expected product is the first of the enantiomers thereby obtained.
  • 18
  • [ 127733-40-8 ]
  • [ 1001088-64-7 ]
  • 19
  • [ 127733-40-8 ]
  • [ 105-34-0 ]
  • C13H10F6N2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
at 20℃;Neat (no solvent); General procedure: In step 1, a mixture of methyl cyanoacetate (25 mmol) and the amine (25 mmol) was stirred vigorously for overnight. The resulting solid was triturated with 8 mL 95% ethanol and the product filtered. The amide from the step1 reaction (5.0 mmol), aldehyde (5 mmol), and piperidine (five drops) were stirred in anhydrous ethanol (10 mL). Ethanol was evaporated and solid was triturated with water and dried under high vacuum to give the desired product.
  • 22
  • [ 1370726-04-7 ]
  • [ 127733-40-8 ]
YieldReaction ConditionsOperation in experiment
77.6 mg With hydrogen; In methanol; at 20℃; for 1.0h; The resulting 1-[3,5-bis(trifluoromethyl)phenyl]ethyl azide (crude product: 111.5 mg) was dissolved in methanol (6 mL) and the solution was added with palladium-fibroin (18 mg) for hydrogen substitution, and then the mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered through Celite, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (chloroform:methanol = 50:1 to 5:1) to obtain 77.6 mg of 1-[3,5-bis(trifluoromethyl)phenyl]ethylamine as colorless oil (yield: 91%, for 2 steps). 1H-NMR (CDCl3) delta: 1.42 (3H, d, J=6.8Hz), 1.58 (2H, br-s), 4.30 (1H, q, J=6.8Hz), 7.75 (1H, s), 7.85 (2H, s) [0118] Specific rotation of the resulting 1-[3,5-bis(trifluoromethyl)phenyl]ethylamine was as follows.[alpha]D25 -15.9 (c = 1.31, CHCl3) [0119] Specific rotation of a commercially available standard product ((S)-1-[3,5-bis(trifluoromethyl)phenyl]ethylamine (Central Glass Co., Ltd., Lot. 0102000, optical purify: 99%ee)) was as follws.[alpha]D25 -15.9 (c = 1.15, CHCl3)
58.9 mg With hydrogen; In methanol; at 20℃; for 1.0h; Example 1-5[0052] The crude product of 1-azido-[3,5-bis(trifluoromethyl)phenyl]ethane obtained in Example 1-4 was added with palladium-fibroin (18 mg) and methanol (6 mL), and after the atmosphere was replaced with hydrogen, the mixture was stirred at room temperature. After stirring over I hour, the reaction mixture was filtered through Celite, and concentrated, and the resulting residue was purified by silica gel column chromatography (chloroform:methanol = 50:1 to 5:1) to obtain 58.9 mg of alpha-[3,5-bis(trifluoromethyl)phenyl]ethylamine as colorless oil.Yield: 74% (for two steps) (S)-alpha-[3,5-bis(trifluoromethyl)phenyl]ethylamine produced by Central Glass Co., Ltd.Lot. 0102000Optical purity, 99%ee
77.6 mg With hydrogen; In methanol; at 20℃; for 1.0h; The obtained 1-[3,5-bis(trifluoromethyl)phenyl]ethyl azide (crude product: 111.5 mg) was dissolved in methanol (6 mL), and palladium fibroin (18 mg) was then added to the obtained solution. Hydrogen substitution was carried out and the mixture was stirred at a room temperature for 1 hour. The reaction solution was filtrated with Celite, and the filtrate was then concentrated under a reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform:methanol=50:1 to 5:1), to obtain 77.6 mg of 1-[3,5-bis(trifluoromethyl)phenyl]ethylamine in the form of a colorless oily product (yield: 91%, 2 steps). 1H-NMR (CDCl3) delta: 1.42 (3H, d, J=6.8 Hz), 1.58 (2H, br-s), 4.30 (1H, q, J=6.8 Hz), 7.75 (1H, s), 7.85 (2H, s)
  • 23
  • [ 368-63-8 ]
  • [ 127733-40-8 ]
  • 24
  • [ 108-24-7 ]
  • [ 127733-40-8 ]
  • [ 1355162-92-3 ]
  • 25
  • (E)-1-(3,5-bis(trifluoromethyl)phenyl)ethanone oxime [ No CAS ]
  • [ 127733-40-8 ]
  • 26
  • [ 1098069-30-7 ]
  • [ 127733-40-8 ]
  • 27
  • [ 1446706-33-7 ]
  • [ 127733-40-8 ]
YieldReaction ConditionsOperation in experiment
77.6 mg With hydrogen; In methanol; at 20℃; for 1.0h; The 1-[3,5-bis(trifluoromethyl)phenyl]ethyl azide (crude product: 111.5 mg) thus obtained was dissolved inmethanol (6 mL), mixed with palladium-fibroin (18 mg), and substituted to hydrogen gas replacement, and stirred for 1hour at room temperature. The solution was filtered through Celite, the filtrate was concentrated under reduced pressure,and the residue thus obtained was purified by silica gel column chromatography (chloroform : methanol = 50:1 to 5:1),thereby obtaining 77.6 mg of1-[3,5-bis (trifluoromethyl)phenyl] ethylamine in the form of a colorless oil (yield: 91%, two steps).[0081] 1H-NMR (CDCl3) delta: 1.42 (3H, d, J = 6.8 Hz), 1.58 (2H, br-s), 4.30 (1H, q, J = 6.8 Hz), 7.75 (1H, s), 7.85 (2H, s) [0082] The specific optical rotation of the 1-[3,5-bis(trifluoromethyl)phenyl]ethylamine thus obtained was as describedbelow.[alpha] D25 -15.9 (c = 1.31, CHCl3) [0083] The specific optical rotation of the commercially available reference standard of((S)-1-[3,5-bis(trifluoromethyl)phenyl]ethylamine (Central Glass Co., Ltd.: Lot. 0102000: optical purity: 99% ee)) was asfollows:[alpha]D25 -15.9 (c = 1.15, CHCl3)[0084] The symbol of the actual specific optical rotation agreed with the symbol of the commercially available referencestandard, indicating that the 1-[3,5-bis(trifluoromethyl)phenyl]ethylamine thus obtained is an (S)-enantiomer. This aminewas prepared from 1-bromo-1-[3,5-bis (trifluoromethyl) phenyl] ethane through the nucleophilic substitution reaction ofazide ion, indicating that the 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane obtained in the above-described 1-(a) isan (R)-enantiomer.
  • 28
  • [ 160376-84-1 ]
  • [ 127733-40-8 ]
  • 30
  • [ 534613-13-3 ]
  • [ 127733-40-8 ]
  • 31
  • 1-[3,5-bis(trifluoromethyl)phenyl]ethylphthalimide [ No CAS ]
  • [ 127733-40-8 ]
  • 32
  • [ 127733-40-8 ]
  • [ 99-33-2 ]
  • N-(1-(3,5-bis(trifluoromethyl)phenyl)ethyl)-3,5-dinitrobenzamide [ No CAS ]
 

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