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Chemical Structure| 133773-29-2 Chemical Structure| 133773-29-2
Chemical Structure| 133773-29-2

(R)-1-(2,4-Dichlorophenyl)ethanamine

CAS No.: 133773-29-2

4.5 *For Research Use Only !

Cat. No.: A905805 Purity: 95%

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Product Details of [ 133773-29-2 ]

CAS No. :133773-29-2
Formula : C8H9Cl2N
M.W : 190.07
SMILES Code : C[C@@H](N)C1=CC=C(Cl)C=C1Cl
MDL No. :MFCD06761788
InChI Key :OUVZHZAOWDHBOU-RXMQYKEDSA-N
Pubchem ID :2496565

Safety of [ 133773-29-2 ]

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

Computational Chemistry of [ 133773-29-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 48.94
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

2.44
Log Po/w (WLOGP)?

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

2.69
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.

3.03
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

2.87
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.67

Water Solubility

Log S (ESOL):?

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

-2.89
Solubility 0.243 mg/ml ; 0.00128 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.

-2.63
Solubility 0.446 mg/ml ; 0.00235 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

-3.71
Solubility 0.0372 mg/ml ; 0.000196 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.

-5.73 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

2.0
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 [ 133773-29-2 ]

* 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 [ 133773-29-2 ]

[ 133773-29-2 ] Synthesis Path-Downstream   1~30

  • 1
  • 3-chloro-3-methyl-1-trifluoromethyl-cyclobutanecarbonyl chloride [ No CAS ]
  • [ 133773-29-2 ]
  • cis-(R)-3-chloro-3-methyl-1-trifluoromethyl-N-[1-(2,4-dichlorophenyl)ethyl]cyclobutanecarboxamide [ No CAS ]
  • trans-(R)-3-chloro-3-methyl-1-trifluoromethyl-N-[1-(2,4-dichlorophenyl)ethyl]cyclobutanecarboxamide [ No CAS ]
  • 2
  • 3-chloro-1,3-dimethyl-cyclobutanecarbonyl chloride [ No CAS ]
  • [ 133773-29-2 ]
  • cis-(R)-3-chloro-1,3-dimethyl-N-[1-(2,4-dichlorophenyl)ethyl]cyclobutanecarboxamide [ No CAS ]
  • 3
  • [ 3218-36-8 ]
  • [ 133773-29-2 ]
  • [ 323179-27-7 ]
YieldReaction ConditionsOperation in experiment
72.9% With hydrogenchloride; sodium hydroxide; sodium borohydrid; In methanol; tert-butyl methyl ether; water; Example 33 7.06 g (37.1 mol) of (R)-2,4-dichloro-alpha-methylbenzylamine and 8.13 g (44.6 mmol) of 4-phenylbenzaldehyde were mixed in 50 ml of t-butyl methyl ether and stirred at room temperature for 1 hour. After ascertaining the disappearance of the amine, 30 ml of methanol was added thereto and 2.60 g (68.7 mmol) of sodium borohydride was gradually added at room temperature and stirred at room temperature for 16 hours. After the reaction, 13 ml of 36% hydrochloric acid and 10 ml of water were added at room temperature and evaporated under reduced pressure to yield crystals. To the obtained crystals was added 25 ml of t-butyl methyl ether, stirred and separated the crystals by filtration. The crystals were washed with 50 ml of t-butyl methyl ether and then mixed with alkaline solution containing 2.87 g of sodium hydroxide in 100 ml of water and extracted with 800 ml of t-butyl methyl ether under alkaline condition. The extract was evaporated under reduced pressure to yield 9.65 g (27.1 mmol) of (R)-N-(4-phenylbenzyl)-2,4dichloro-alpha-methylbenzylamine. (Yield: 72.9%, Purity 99.1%); NMR spectrum data (delta ppm, CDCl3); 1.34 (d) 3H; 1.60 (s) 1H; 3.64 (s) 2H; 4.32 (q) 1H; 7.25-7.62 (m) 12H.
YieldReaction ConditionsOperation in experiment
(1) A solution consisting of 16 g of (RS)-1-(2,4-dichlorophenyl)ethylamine and 10 ml of ethanol was heated to 70 C. while stirring, a solution consisting 12.8 g of L-mandelic acid and 40 ml of ethanol was added thereto over 30 minutes, and a temperature was raised to 75 C., followed by stirring at the same temperature for 30 minutes. After cooling to 20 C. over 5 hours, the precipitated crystals were filtered and dried to obtain 13.2 g of diastereomer salt. 10 g of a 20% aqueous sodium hydroxide solution was added to the crystals, followed by extraction twice with 20 ml of toluene. The resulting organic layer was dried over magnesium sulfate, and the solvent was distilled off to obtain 7.3 g of (R)-1-(2,4-dichlorophenyl)ethylamine. This had the optical purity of 82%ee.
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YieldReaction ConditionsOperation in experiment
With chiral stationary phase including isopropyl-functionalized CF6; In methanol; acetic acid; triethylamine; acetonitrile; at 20℃;Purification / work up; In addition to the foregoing, numerous other chromatographic separations using a column bonded with a CSP including a derivatized cyclofructan residue were carried out. Tables 5-9 list some additional examples of chromatographic separations using a column bonded with a CSP of the present invention. AU examples of chromatographic separations using columns bonded with CSPs of the present invention were carried out using the following experimental conditions and procedures.|0132| The high performance liquid chromatography (HPLC) column packing system was composed of an air driven fluid pump (HASKEL, DSTV- 122), an air compressor, a pressure regulator, a low pressure gauge, two high-pressure gauges (10,000 and 6,000 psi), a slurry chamber, check valves, and tubings. The CSPs were slurry packed into a 25 cm x 0.46 cm (inner diameter, I. D.) stainless steel column.|0133| The HPLC system was an Agilent 1 100 system (Agilent Technologies, Palo Alto,CA), which consisted of a diode array detector, an autosampler, a binary pump, a temperature- controlled column chamber, and Chemstation software. All chiral analytes were dissolved in ethanol, methanol, or other appropriate mobile phases, as indicated. For the LC analysis, the injection volume and flow rate were 5 muL and 1 mL/min, respectively. Separations were carried out at room temperature (~20 0C) if not specified otherwise. The wavelengths of UV detection were 195, 200, 210, and 254 nm. The mobile phase was degassed by ultrasonication under vacuum for 5 min. Each sample was analyzed in duplicate. Three operation modes (the normal phase mode, polar organic mode, and reversed phase mode) were tested, unless indicated otherwise. In the normal phase mode, heptane with ethanol or isopropanol was used as the mobile phase. In some cases, trifluoroacetic acid (TFA) was used as an additive, as indicated. The mobile phase of the polar organic mode was composed of acetonitrile/methanol and small amounts of acetic acid and triethylamine. Water/acetonitrile or acetonitrile/acetate buffer (20 mM, pH = 4.1 ) was used as the mobile phase in the reversed-phase mode.|0134| Two different supercritical fluid chromatographic instruments were used. One was a Berger SFC unit with an FCM 1200 flow control module, a TCM 2100 thermal column module, a dual pump control module, and a column selection valve. The flow rate was 4 mL/min. The cosolvent was composed of methanol/ethanol/isopropanol = 1 : 1 : 1 and 0.2% diethylamine (DEA). The gradient mobile phase composition was 5% cosolvent hold during 0- 0.6 min, 5-60% during 0.6-4.3 min, 60% hold during 4.3-6.3 min, 60%-5% during 6.3-6.9 min, and 5% hold during 6.9-8.0 min. The other SFC system was a Jasco (MD, USA) system comprised of an autosampler unit (AS-2059-SF Plus), a dual pump module (PU-2086 Plus), a column thermostat module (CO-2060 Plus), a UV/Vis detector (UV-2075 Plus), and a back pressure regulator module (SCH-Vch-BP). Unless otherwise specified, the mobile phase was composed of CCVmethanol (0.1 % TFA or 0.1% diethylamine). The flow rate was 3 mL/min.|0135| For the calculations of chromatographic data, the "dead time" to was determined by the peak of the refractive index change due to the sample solvent or determined by injecting l ,3,5-tri-/e/-/-butylbenzene in the normal phase mode.
  • 6
  • [ 178306-51-9 ]
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YieldReaction ConditionsOperation in experiment
93.09% In acetonitrile; for 1.75h;Reflux;Product distribution / selectivity; In a 5 liter three necked flask, (302 g) (1.10 mole) 3,3-diphenyl-2-hydroxy-3-methoxy propanoic acid and 3.02 liter acetonitrile was taken. Subsequently, the reaction mixture was stirred and heated at reflux temperature. (105.4 g) (0.55 mole) (R)-2,4-dichloro PEA, in 50 mL acetonitrile was added drop wise in 45 min. time interval Solid material was precipitated during this addition. The reaction mixture was stirred under reflux for 1 hr and cooled to room temperature. The reaction mixture was further stirred at room temperature for 1 hour. Solid material was filtered, washed with acetonitrile and dried. Yield: 219 g, (85.41%), HPLC purity: 99.94%, Chiral purity: 95.01%. Similarly, different diastereomeric salt of (S)-2-hydroxy-3-methoxy 3,3-diphenyl propionate was prepared using different chiral amine in different batches and the results are summarized in Table 2 given below
60% In acetonitrile;Resolution of racemate;Product distribution / selectivity; Similarly, different diastereomeric salt of (S)-2-hydroxy-3 -methoxy 3, 3-diphenyl propionate was prepared using different chiral amine in different batches and the results are summarized in Table 2 given below.Table 2;* Input refers to 3, 3-diphenyl-2-hydroxy-3-methoxy propionic acid
  • 7
  • [ 321-23-3 ]
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  • [ 1442445-21-7 ]
YieldReaction ConditionsOperation in experiment
94% With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 1h; a) To a solution of 4-bromo-2-fluoro-nitrobenzene (5.8 g, 25.6 mmol) and (lR)-l- (2,4-dichlorophenyl)ethanamine (prepared from Example 1, 5.1 g, 26.8 mmol) in anhydrous dimethyl sulfoxide (DMSO, 55 mL) was added potassium carbonate (K2CO3, 7.4 g, 53.1 mmol). The reaction mixture was heated at 120 C for 1 h. After cooling to room temperature, the mixture was diluted with deionized water (750 mL) and the flask was rinsed with z'PrOH (25 mL). The mixture was stirred for 30 min, and a bright yellow solid was obtained. The solid was collected by filtration, and dried in vacuo to give the desired product (9.7 g, 25.0 mmol, 94%). MS: (ES) m/z calculated for Ci4H12BrCl2 202 [M + H]+ 388.9, found 390.
  • 8
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  • [ 133773-29-2 ]
YieldReaction ConditionsOperation in experiment
40% Example 1: Resolution of (l ?)-l-(2,4-dichlorophenyl)ethanamine 60 C, 2 crystallizations 2) 4 M NaOH >96% ee 40% [0115] (5)-Mandelic acid (40.2 g, 264.5 mmol) was added to a solution of 3:2 isopropyl alcohol ( PrOH) and ethanol (EtOH, 500 mL) at room temperature, and the suspension was heated at 60 C until a clear solution formed. Racemic 2,4-dichloro- -methyl benzylamine (50 g, 264.5 mmol) was added to the hot solution, which was then cooled to 30 C over 2 h and stirred at this temperature for 24 h. The colorless crystals were collected by filtration and washed with acetone (70 mL). The resulting salt (37.3 g, -90% ee, determined by Mosher's method, J. Am. Chem. Soc, 1973, 95, 512.) was suspended in 3 :2 PrOH/EtOH (400 mL) at room temperature and the mixture was heated at 60 C to give a clear solution. The solution was then cooled to room temperature and stirred for 24 h. The colorless crystals were filtered off, and washed with acetone (40 mL) to give the desired salt (32.0 g, >96% ee, determined by Mosher's method). To a portion of the salt (12.0 g) in dichloromethane ((?(? 100 mL) was added 4 M aqueous sodium hydroxide solution (30 mL). The reaction mixture was stirred for 1 h at room temperature, and extracted with dichloromethane (2 x 100 mL), dried with anhydrous sodium sulfate ( a2S04), filtered, and concentrated in vacuo to afford (lR)-l- (2,4-dichlorophenyl)ethanamine as a colorless liquid (7.5 g, 39.5 mmol, 40%).
40% (5)-Mandelic acid (40.2 g, 264.5 mmol) was added to a solution of 3:2 isopropyl alcohol (/PrOH) and ethanol (EtOH) (500 mL) at room temperature, and the suspension was heated at 60 C until a clear solution formed. Racemic 2,4-dichloro-a-methyl benzylamine (50 g, 264.5 mmol) was added to the hot solution, which was then cooled to 30 C over 2 h and stirred at this temperature for 24 h. The colorless crystals were collected by filtration and washed with acetone (70 mL). The resulting salt (37.3 g, ~90% ee, determined by Mosher's method, J. Am. Chem. Soc, 1973, 95, 512.) was suspended in 3:2 /PrOH/EtOH (400 mL) at room temperature and the mixture was heated at 60 C to give a clear solution. The solution was then cooled to room temperature and stirred for 24 h. The colorless crystals were filtered off, and washed with acetone (40 mL) to give the desired salt (32.0 g, >96% ee, determined by to Mosher's method). To a portion of the salt (12.0 g) in dichloromethane (CH2C12) (100 mL) was added aqueous 4 N sodium hydroxide solution (30 mL). The reaction mixture was stirred for 1 h at room temperature, and extracted with dichloromethane (2 chi 100 mL), dried with anhydrous sodium sulfate (Na2S04), filtered, and concentrated in vacuo to afford (li?)-l- (2,4-dichlorophenyl)ethanamine as a colorless liquid (7.5 g, 39.5 mmol, 40%).
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  • (4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)piperazin-1-yl)((R)-pyrrolidin-2-yl)methanone dihydrochloride [ No CAS ]
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