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Chemical Structure| 34351-19-4 Chemical Structure| 34351-19-4

Structure of 34351-19-4

Chemical Structure| 34351-19-4

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Product Details of [ 34351-19-4 ]

CAS No. :34351-19-4
Formula : C10H13Cl2NO
M.W : 234.12
SMILES Code : N[C@@H](CC1=CC=CC=C1)C(CCl)=O.[H]Cl
MDL No. :MFCD00133443
InChI Key :DLNJXAGVYFIVJM-FVGYRXGTSA-N
Pubchem ID :56777393

Safety of [ 34351-19-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P301+P330+P331-P303+P361+P353-P363-P304+P340-P310-P321-P260-P264-P280-P305+P351+P338-P405-P501
Class:8
UN#:1759
Packing Group:

Computational Chemistry of [ 34351-19-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.3
Num. rotatable bonds 4
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 60.5
TPSA ?

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

43.09 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

2.45
Log Po/w (WLOGP)?

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

2.17
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.

2.05
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

2.34
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.8

Water Solubility

Log S (ESOL):?

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

-2.89
Solubility 0.303 mg/ml ; 0.00129 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.

-3.0
Solubility 0.235 mg/ml ; 0.001 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

-3.46
Solubility 0.0802 mg/ml ; 0.000343 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.

-5.99 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

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)

1.9

Application In Synthesis of [ 34351-19-4 ]

* 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 [ 34351-19-4 ]

[ 34351-19-4 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 102123-74-0 ]
  • [ 34351-19-4 ]
YieldReaction ConditionsOperation in experiment
98% With hydrogenchloride; In water; ethyl acetate; at 0 - 20℃; (S)-4-Chloro-3-oxo-l-phenylbutan-2-aminiumchloride (8). Ketone 1 (5.00 g, 16.8 mmol) was dissolved in EtOAc (50 mL) and cooled to 0°C in an ice bath. Concentrated HC1 (15.3 mL, 503 mmol) was added dropwise to the solution. Upon complete addition of the acid, the ice bath was removed and the solution was stirred at room temperature for 1 hour. The white solid was filtered and washed with EtOAc and Et20 to give pure salt 8 (3.85 g, 16.4 mmol, 98percent): mp 170-172°C (lit mp 170°C); 1H NMR delta 3.17 (m, 2H), 4.51 (s, 1H), 4.62 (2H), 7.31 (m, 5H), 8.69 (s, 3H); 13C NMR 8 35.0, 48.0, 57.2, 127.4, 128.9, 129.5, 134.5, 198.3; LRMS (ES+) calcd for Ci0Hi3NOCl2 234.12, found 198.2 (CioHi3NOCl); Elemental analysis calcd for C10H13NOC12: C 51.30, H 5.60, N 5.98; found: C 54.41, H 5.62, N 6.01.
  • 2
  • [ 24424-99-5 ]
  • [ 34351-19-4 ]
  • [ 102123-74-0 ]
  • 2,5-dibenzyl-3-chloromethyl-6-methyl-pyrazine [ No CAS ]
  • 3
  • [ 24424-99-5 ]
  • [ 34351-19-4 ]
  • [ 102123-74-0 ]
YieldReaction ConditionsOperation in experiment
85% With sodium chloride; triethylamine; In dichloromethane; water; Example 13 Process for producing (3S)-3-tert-butoxycarbonylamino-1-chloro-4-phenyl-2-butanone Di-tert-butyl dicarbonate (85.8 mg) and triethylamine (29.1 mg) were dissolved in methylene chloride (2.6 ml), and an aqueous solution of (3S)-3-amino-1-chloro-4-phenyl-2-butanone hydrochloride (61.4 mg) in water (2.6 ml) was added thereto dropwise. The mixture was stirred at room temperature for 1 hour, then heated at 40° C., and further reacted for 1.5 hours. After the reaction solution was cooled to room temperature, a sodium chloride aqueous solution was added thereto, and the mixture was extracted twice with ethyl acetate. The resulting ethyl acetate layer was analyzed by HPLC, and it was identified that (3S)-3-tert-butoxycarbonylamino-1-chloro-4-phenyl-2-butanone (66.3 mg) was obtained in a yield of 85percent.
81% With sodium chloride; triethylamine; In toluene; Example 15 Process for producing (3S)-3-tert-butoxycarbonylamino-1-chloro-4-phenyl-2-butanone Di-tert-butyl dicarbonate (4.64 g) and triethylamine (5.28 ml) were dissolved in toluene (81.9 ml), and an aqueous solution (45.60 g) of (3S)-3-amino-1-chloro-4-phenyl-2-butanone hydrochloride (3.83 g) was added thereto dropwise over 10 minutes. The solution was stirred at room temperature for 1 hour, then heated at 40° C., and further reacted for 1 hour. After the reaction solution was cooled to room temperature, the aqueous layer was separated. The resulting toluene layer was washed with 2 N hydrochloric acid and with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. Then, magnesium sulfate was removed. The resulting toluene layer was analyzed by HPLC, and it was identified that (3S)-3-tert-butoxycarbonylamino-1-chloro-4-phenyl-2-butanone (3.94 g) was obtained in a yield of 81percent.
81% With triethylamine; In toluene; EXAMPLE 7 Process for Producing (3S)-3-tert-butoxycarbonylamino-1-chloro-4-phenyl-2-butanone Di-tert-butyl dicarbonate (4.64 g) and triethylamine (5.28 ml) were dissolved in toluene (81.9 ml). An aqueous solution (45.60 g) of (3S)-3-amino-1-chloro-4-phenyl-2-butanone hydrochloride (3.83 g) was added dropwise to the obtained solution for a period of 10 minutes. After stirring at room temperature for 1 hour, the reaction mixture was heated to 40° C. and the reaction was conducted for additional 1 hour. The reaction mixture was cooled to room temperature, and the aqueous layer was separated. The resultant toluene layer was washed with 2 N hydrochloric acid and saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. Magnesium sulfate was removed. The obtained toluene layer was analyzed by HPLC to find that (3S)-3-tert-butoxycarbonylamino-1-chloro-4-phenyl-2-butanone (3.94 g) was obtained in a yield of 81percent.
75% With N-ethyl-N,N-diisopropylamine; In toluene; Example 16 Process for producing (3S)-3-tert-butoxycarbonylamino-1-chloro-4-phenyl-2-butanone Di-tert-butyl dicarbonate (1.20 g) and diisopropylethylamine (2.65 ml) were dissolved in toluene (11.5 ml), and an aqueous solution (11.27 g) of (3S)-3-amino-1-chloro-4-phenyl-2-butanone hydrochloride (1.00 g) was added thereto dropwise over 35 minutes. The mixture was reacted overnight at room temperature by being stirred, and the aqueous layer was then separated. The resulting toluene layer was washed with an aqueous solution of 1 mol/liter of citric acid and with water. The resulting toluene layer was analyzed by HPLC, and it was identified that (3S)-3-tert-butoxycarbonylamino-1-chloro-4-phenyl-2-butanone (0.95 g) was obtained in a yield of 75percent.
70% With sodium hydrogencarbonate; In methanol; hexane; Example 12 Process for producing (3S)-3-tert-butoxycarbonylamino-1-chloro-4-phenyl-2-butanone Di-tert-butyl dicarbonate (1.39 g) and sodium hydrogencarbonate (0.34 g) were dissolved in a 50percent methanol aqueous solution (22 ml), and an aqueous solution of (3S)-3-amino-1-chloro-4-phenyl-2-butanone hydrochloride (0.94 g) was added thereto. The mixture was stirred at 40° C. for 1.5 hours. The reaction solution was extracted twice with ethyl acetate, the resulting ethyl acetate layer was dried over anhydrous magnesium sulfate, and magnesium sulfate was removed. The ethyl acetate layer was concentrated, and crystallized by adding hexane thereto. Crystals precipitated were collected by filtration, and dried to obtain (3S)-3-tert-butoxycarbonylamino-1-chloro-4-phenyl-2-butanone (0.84 g) in a yield of 70percent. Further, the crystals obtained and the reaction solution were analyzed by HPLC using an optically active column, and it was identified that the optical purity thereof was >99.5percente.e., and that a series of reactions proceeded while maintaining the optical purity of L-phenylalanine methyl ester hydrochloride. 1H-NMR(CDCl3) deltappm: 1.41 (s, 9H), 3.00 (dd, J=6.9, 13.8 Hz), 3.08 (dd, J=6.9, 13.8 Hz, 1H), 3.98 (d, J=16.2 Hz, 1H), 4.17 (d, J=16.2 Hz, 1H), 4.68 (q, J=6.9 Hz, 1H), 5.02 (bd, J=6.9 Hz, 1H), 7.16 (m, 2H), 7.26-7.36 (m, 3H) mass spectrum m/e: 296.1 (M-H-)
70% With sodium hydrogencarbonate; In methanol; EXAMPLE 3 Process for Producing (3S)-3-tert-butoxycarbonylamino-1 -chloro-4-phenyl-2-butanone Di-tert-butyl dicarbonate (1.39 g) and sodium hydrogencarbonate (0.34 g) were dissolved in 50percent aqueous methanol solution (22 ml). An aqueous solution of (3S)-3-amino-1-chloro-4-phenyl-2-butanone hydrochloride (0.94 g) was added to the obtained solution, and they were stirred at 40° C. for 1.5 hours. After the extraction with ethyl acetate twice, the obtained ethyl acetate layer was dried over anhydrous magnesium sulfate. Magnesium sulfate was removed. The solvent was evaporated under reduced pressure. Crystals formed by the crystallization with ethyl acetate and hexane were taken by filtration and then dried to obtain (3S)-3-tert-butoxycarbonylamino-1-chloro-4-phenyl-2-butanone (0.84 g) in a yield of 70percent. The obtained crystals and the reaction mixture were analyzed by HPLC with an optically active column to confirm that the product had an optical purity of >99.5percent e.e. 1H-NMR(CDCl3, 300 MHz) delta ppm: 1.41 (s, 9H), 3.00(dd, J=6.9, 13.8 Hz), 3.08 (dd, J=6.9, 13.8 Hz, 1H), 3.98 (d, J=16.2 Hz, 1H), 4.17 (d, J=16.2 Hz, 1H), 4.68 (q, J=6.9 Hz, 1H), 5.02 (bd, J=6.9 Hz, 1H), 7.16 (m, 2H), 7.26-7.36 (m, 3H) mass spectrum m/e: 296.1 (M-H-)

 

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