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Structure of 7691-28-3

Chemical Structure| 7691-28-3

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Product Details of [ 7691-28-3 ]

CAS No. :7691-28-3
Formula : C4H7BrO3
M.W : 183.00
SMILES Code : O=C(OC)C(Br)CO
MDL No. :MFCD20486781
InChI Key :GVXAFLUDYYQGCG-UHFFFAOYSA-N
Pubchem ID :11964350

Safety of [ 7691-28-3 ]

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

Computational Chemistry of [ 7691-28-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 0.75
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 31.66
TPSA ?

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

46.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.37
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

0.26
Log Po/w (WLOGP)?

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

-0.08
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.

0.21
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

0.35
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.42

Water Solubility

Log S (ESOL):?

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

-0.94
Solubility 21.0 mg/ml ; 0.115 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.

-0.8
Solubility 29.1 mg/ml ; 0.159 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

-0.69
Solubility 37.6 mg/ml ; 0.206 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

No
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.

-7.23 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

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)

2.3

Application In Synthesis of [ 7691-28-3 ]

* 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.

  • Upstream synthesis route of [ 7691-28-3 ]

[ 7691-28-3 ] Synthesis Path-Upstream   1~8

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  • [ 160732-12-7 ]
  • [ 7691-28-3 ]
YieldReaction ConditionsOperation in experiment
87% With hydrogen bromide In water at 65℃; for 21 h; Inert atmosphere Synthesis of Methyl 2-Bromo-3-hydroxypropionate
Methyl 2-Bromo-3-hydroxypropionate was synthesized in 68-87percent yield as in the following example. example. A solution of 20 2-bromo-3-hydroxypropionic acid (6.0 g, 35 mmol) and a catalytic amount of 24 HBr (0.2 mL, 48percent aq. w/w) in 36 methanol (50 mL, 1.2 mol) was heated at 65° C. for 21 h. Excess methanol was then removed by rotary evaporation. 37 CH2Cl2 (100 mL) was added to the brownish liquid residue and the resulting solution was washed twice with dilute aq. NaHCO3 (50 mL) and once with 50 mL of satd. NaCl aq. soln., and then dried over Na2SO4. After filtration and removing the solvent by rotary evaporation 34 methyl 2-bromo-3-hydroxypropionate was obtained as a light yellow liquid. Product (5.7 g, 87percent) as a clear liquid was obtained by purification by silica gel chromatography using CH2Cl2/ethyl ether (90/10) with Rf=0.31. 1H NMR (CDCl3): 2.70 (br s, OH), 3.81 (CH3), 4.00 (m, CH2OH), 4.35 (t, CHBr). 13C NMR (CDCl3): 44.2 (CBr), 53.5 (CH3), 63.8 (CH2OH), 169.7 (CO2CH3). Anal. C, H: calcd. 26.23, 3.86; found 25.83, 4.10.
References: [1] Synlett, 2010, # 13, p. 1947 - 1950.
[2] Patent: US8524942, 2013, B2, . Location in patent: Page/Page column 17.
[3] Journal of Biological Chemistry, 1934, vol. 105, p. 547,551.
[4] Patent: US2016/287726, 2016, A1, . Location in patent: Paragraph 0081; 0082.
  • 2
  • [ 67-56-1 ]
  • [ 56-45-1 ]
  • [ 7691-28-3 ]
YieldReaction ConditionsOperation in experiment
65%
Stage #1: With bromic acid; potassium bromide; sodium nitrite In water at -10 - 20℃;
Stage #2: With bromic acid In water at 65℃; for 48 h;
[1496] Step 2: methyl 2-bromo-3-hydroxypropanoate[1497] To a solution of L-serine (5.0 g, 47.6 mmol), a 48 w/wpercent bromic acid solution (13.0 mL, 109.5 mmol), and potassium bromide (20.0 g, 157.1 mmol) in water (44.0 mL) was added portionwise sodium nitrite (6.0 g, 80.9 mmol) at -10 ℃. The reaction mixture was stirred at room temperature overnight. The reaction mixture was saturated with sodium chloride and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and then evaporated. The residue was dissolved in methanol (50.0 mL) and then 48 w/wpercent bromic acid (0.2 mL) was added thereto. The reaction mixture was stirred at 65 ℃ for 2 days and then concentrated under reduced pressure to discard excess methanol. The resulting dark yellow residue was dissolved in dichloromethane (100.0 mL) and then washed with a saturated sodium hydrogen carbonate solution (50.0 mL) and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and then evaporated. The residue was dried under reduced pressure to give 5.7 g of the titled compound (Yield: 65percent).[1498] 1H NMR (CDCl3, 400 MHz) δ 4.36(t, 1H), 4.01-4.08(m, 1H), 3.93-3.97(m, 1H), 3.82(s, 3H), 2.56(t, 1H)
65%
Stage #1: With bromic acid; potassium bromide; sodium nitrite In water at -10 - 20℃;
Stage #2: at 65℃; for 48 h;
Step 2:
methyl 2-bromo-3-hydroxypropanoate
To a solution of L-serine (5.0 g, 47.6 mmol), a 48 w/w percent bromic acid solution (13.0 mL, 109.5 mmol), and potassium bromide (20.0 g, 157.1 mmol) in water (44.0 mL) was added portionwise sodium nitrite (6.0 g, 80.9 mmol) at -10° C.
The reaction mixture was stirred at room temperature overnight.
The reaction mixture was saturated with sodium chloride and then extracted with ethyl acetate.
The organic layer was dried over anhydrous magnesium sulfate, filtered, and then evaporated.
The residue was dissolved in methanol (50.0 mL) and then 48 w/w percent bromic acid (0.2 mL) was added thereto.
The reaction mixture was stirred at 65° C. for 2 days and then concentrated under reduced pressure to discard excess methanol.
The resulting dark yellow residue was dissolved in dichloromethane (100.0 mL) and then washed with a saturated sodium hydrogen carbonate solution (50.0 mL) and brine.
The organic layer was dried over anhydrous sodium sulfate, filtered, and then evaporated.
The residue was dried under reduced pressure to give 5.7 g of the titled compound (Yield: 65percent).
1H NMR (CDCl3, 400 MHz) δ 4.36 (t, 1H), 4.01-4.08 (m, 1H), 3.93-3.97 (m, 1H), 3.82 (s, 3H), 2.56 (t, 1H)
References: [1] Patent: WO2013/43001, 2013, A1, . Location in patent: Paragraph 1496; 1497; 1498.
[2] Patent: US2015/11528, 2015, A1, . Location in patent: Paragraph 0818-0819.
  • 3
  • [ 292638-85-8 ]
  • [ 7691-28-3 ]
References: [1] Journal of Organic Chemistry, 2006, vol. 71, # 20, p. 7533 - 7537.
[2] Patent: US2446651, 1944, , .
[3] Journal of Biological Chemistry, 1946, vol. 165, p. 501.
[4] Chemical and Pharmaceutical Bulletin, 1974, vol. 22, # 7, p. 1646 - 1651.
[5] Journal of Agricultural and Food Chemistry, 1995, vol. 43, # 4, p. 867 - 871.
  • 4
  • [ 160732-12-7 ]
  • [ 7691-28-3 ]
References: [1] Patent: US2011/46334, 2011, A1, .
  • 5
  • [ 1729-67-5 ]
  • [ 292638-85-8 ]
  • [ 7691-28-3 ]
References: [1] Patent: US4182718, 1980, A, .
  • 6
  • [ 186581-53-3 ]
  • [ 160732-12-7 ]
  • [ 7691-28-3 ]
References: [1] Journal of Organic Chemistry, 1967, vol. 32, p. 244 - 246.
  • 7
  • [ 292638-85-8 ]
  • [ 1729-67-5 ]
  • [ 7691-28-3 ]
  • [ 32777-05-2 ]
References: [1] Bulletin of the Chemical Society of Japan, 1984, vol. 57, # 5, p. 1394 - 1400.
[2] Bulletin of the Chemical Society of Japan, 1984, vol. 57, # 5, p. 1394 - 1400.
  • 8
  • [ 292638-85-8 ]
  • [ 7691-28-3 ]
  • [ 32777-05-2 ]
References: [1] Synlett, 2010, # 13, p. 1947 - 1950.
 

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