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Chemical Structure| 55666-43-8 Chemical Structure| 55666-43-8

Structure of tert-Butyl 3-bromopropanoate
CAS No.: 55666-43-8

Chemical Structure| 55666-43-8

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Product Details of [ 55666-43-8 ]

CAS No. :55666-43-8
Formula : C7H13BrO2
M.W : 209.08
SMILES Code : O=C(OC(C)(C)C)CCBr
MDL No. :MFCD04974087
InChI Key :RMWVUWLBLWBQDS-UHFFFAOYSA-N
Pubchem ID :256128

Safety of [ 55666-43-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H227-H302-H315-H319-H335
Precautionary Statements:P210-P261-P264-P270-P271-P280-P301+P312+P330-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P370+P378-P403+P233-P403+P235-P405-P501

Computational Chemistry of [ 55666-43-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.86
Num. rotatable bonds 4
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 44.96
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.58
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

1.79
Log Po/w (WLOGP)?

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

2.11
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.

2.12
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

1.81
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.08

Water Solubility

Log S (ESOL):?

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

-2.0
Solubility 2.09 mg/ml ; 0.01 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.

-1.96
Solubility 2.29 mg/ml ; 0.0109 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

-2.45
Solubility 0.745 mg/ml ; 0.00356 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.

-6.3 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)

2.12

Application In Synthesis of [ 55666-43-8 ]

* 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 [ 55666-43-8 ]

[ 55666-43-8 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 55666-43-8 ]
  • [ 64628-73-5 ]
  • [ 1290048-34-8 ]
YieldReaction ConditionsOperation in experiment
60% With 2,6-dimethylpyridine; In toluene; for 48h;Reflux; A solution of 9.26 g (42.4 mmol) of <strong>[64628-73-5]3-chloro-4-trifluoromethoxy-phenylamine</strong> and 4.39 ml (42.4 mmol) of 2,6-lutidine in 50 ml of toluene was treated slowly with 7.30 ml (42.4 mmol) of tert-butyl 3-bromopropionate and stirred 2 days at reflux temperature. The reaction was then partitioned between aqueous 10% KHS04 and EtOAc (3x). The organic phases were washed with 10%> NaCl, dried over Na2S04 evaporated and purified by flash silica gel column (n -heptane :EtO Ac 9:1) to yield 9.59 g (60%>) of the title compound as brown liquid. MS: 339 (M+, CI).
60% With 2,6-dimethylpyridine; In toluene; for 48h;Reflux; A) 3-(3-Chloro-4-trifluoromethoxy-phenylamino)-propionic acid tert-butyl ester A solution of 9.26 g (42.4 mmol) of <strong>[64628-73-5]3-chloro-4-trifluoromethoxy-phenylamine</strong> and 4.39 ml (42.4 mmol) of 2,6-lutidine in 50 ml of toluene was treated slowly with 7.30 ml (42.4 mmol) of tert-butyl 3-bromopropionate and stirred 2 days at reflux temperature. The reaction was then partitioned between aqueous 10% KHSO4 and EtOAc (3*). The organic phases were washed with 10% NaCl, dried over Na2SO4 evaporated and purified by flash silica gel column (n-heptane:EtOAc 9:1) to yield 9.59 g (60%) of the title compound as brown liquid. MS: 339 (M+, Cl).
  • 2
  • [ 55666-43-8 ]
  • [ 75279-55-9 ]
  • (+/-)-tert-butyl 4-(2-chloro-6-fluorophenyl)-4-cyanobutanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
41% [0585] To a solution of (2-chloro-6-fluorophenyl)acetonitrile (2.00 g, 11.8 mmol) in THF (15 ml) under argon was added gradually while stirring, at -78C., a 2 M solution of LDA in THF (8.8 ml, 18 mmol). The mixture was allowed to come to 0C. and, after 15 min, cooled back down again to -78C. Subsequently, tert-butyl 3-bromopropanoate (2.2 ml, 14 mmol) was slowly added dropwise thereto at -78C. while stirring. Stirring of the mixture was continued overnight, in the course of which the cooling bath (dry ice/acetone) was allowed to come gradually to RT. Subsequently, water was added gradually to the mixture, which was extracted twice with ethyl acetate. The combined organic phases were washed once with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated, and the residue was prepurified by flash column chromatography (50 g silica gel Biotage Snap-Cartridge KP-Sil, cyclohexane/ethyl acetate gradient 93:7→6:4, Isolera One). This was followed by repurification by preparative HPLC (Method 16). The combined target fractions were concentrated and the residue was dried under reduced pressure. This gave 1.45 g (100% purity, 41% of theory) of the title compound. [0586] LC-MS (Method 1): Rt=2.16 min; MS (ESIpos): m/z=298 [M+H]+
  • 3
  • [ 55666-43-8 ]
  • [ 326-62-5 ]
  • (+/-)-tert-butyl 4-cyano-4-(2-fluorophenyl)butanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
4.22 g [0604] To a solution of <strong>[326-62-5](2-fluorophenyl)acetonitrile</strong> (5.00 g, 37.0 mmol) in THF (35 ml) under argon was added gradually while stirring, at -78C., a 2 M solution of LDA in THF (22 ml, 44 mmol). The mixture was allowed to come to 0C. and, after 15 min, cooled back down again to -78C. Subsequently, a solution of tert-butyl 3-bromopropanoate (7.0 ml, 44 mmol) in THF (10 ml) was slowly added dropwise thereto at -78C. while stirring. Stirring of the mixture was continued overnight, in the course of which the cooling bath (dry ice/acetone) was allowed to come gradually to RT. Subsequently, water and ethyl acetate (100 ml of each) were gradually added at about 0C. to the mixture, which was agitated. After phase separation, the aqueous phase was extracted once with ethyl acetate (100 ml). The combined organic phases were washed once with saturated aqueous sodium chloride solution (150 ml), dried over sodium sulfate, filtered and concentrated, and the residue was taken up in dichloromethane and purified by flash column chromatography (100 g silica gel Biotage Snap-Cartridge Ultra, cyclohexane/ethyl acetate gradient 93:7?7:3, Isolera One). The combined target fractions were concentrated and the residue was dried under reduced pressure. This gave 4.22 g (69% purity, 29% of theory) of the title compound. [0605] LC-MS (Method 1): Rt=2.08 min; MS (ESIpos): m/z=264 [M+H]+
 

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Technical Information

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