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Chemical Structure| 61940-21-4 Chemical Structure| 61940-21-4

Structure of 61940-21-4

Chemical Structure| 61940-21-4

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Product Details of [ 61940-21-4 ]

CAS No. :61940-21-4
Formula : C9H8BrNO4
M.W : 274.07
SMILES Code : O=C(OC)C1=C([N+]([O-])=O)C=CC=C1CBr
MDL No. :MFCD04114314
Boiling Point : No data available
InChI Key :SJJJFLXTGHEZJB-UHFFFAOYSA-N
Pubchem ID :21708527

Safety of [ 61940-21-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H314
Precautionary Statements:P260-P264-P270-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P405-P501
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 61940-21-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 4
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 59.38
TPSA ?

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

72.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.79
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

1.27
Log Po/w (WLOGP)?

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

2.12
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.

1.61
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

0.6
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.48

Water Solubility

Log S (ESOL):?

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

-2.37
Solubility 1.17 mg/ml ; 0.00425 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.

-2.38
Solubility 1.13 mg/ml ; 0.00413 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

-3.11
Solubility 0.213 mg/ml ; 0.000776 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

Yes
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.

-7.07 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

3.0 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)

2.43

Application In Synthesis of [ 61940-21-4 ]

* 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 [ 61940-21-4 ]

[ 61940-21-4 ] Synthesis Path-Downstream   1~4

  • 2
  • [ 608141-42-0 ]
  • [ 61940-21-4 ]
  • [ 1227368-31-1 ]
YieldReaction ConditionsOperation in experiment
93% With potassium carbonate; In acetonitrile; at 81 - 83℃; for 2h;Product distribution / selectivity; Example 4B Alternative Preparation of Compound (1)Compound (1) was also prepared by the following procedure. A mixture of methyl 2-bromomethyl-6-nitrobenzoate (100.0 g, 365 mmol, prepared previously in Example 2), <strong>[608141-42-0](1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine</strong> (104.7 g, 383 mmol, prepared previously in Example 3), and potassium carbonate powder (100.8 g, 730 mmol, from Aldrich Chemicals) was suspended in acetonitrile (500 mL) at room temperature. The reaction mixture was refluxed at 81-83 C. for about two hours until there was less than 2% of unreacted methyl 2-bromomethyl-6-nitrobenzoate. After the reaction mixture was cooled to 45-50 C., methanol (200 mL) was charged over 5-10 minutes. After the mixture was allowed to cool to 20-25 C. and stirred for 2 hours, deionized water (1.40 L) was charged over 0.5-1 hour and stirred at 20-25 C. for 30 minutes and at 0-5 C. for 1-2 hours. The solid was filtered, washed with deionized water (3×300 mL), and dried to <10% of water content as measured by Karl Fisher titration. The solid was suspended in methanol (750 mL) and refluxed for 1-1.5 hours. The suspension was cooled to 0-5 C. over 1.5-2 hours and kept at 0-5 C. for 1-1.5 hours. The solid was filtered, washed with 0-5 C. methanol (2×200 mL) and heptane (200 mL), and then dried at 40-45 C. under vacuum to a constant weight. The yield of Compound (1) was 148.0 g (93%), based on 100.0 g input of methyl 2-bromomethyl-6-nitrobenzoate. The product was found to have a purity of >99% measured by HPLC based on area percentage, and a water content of <1.0% measured by Karl Fisher titration.
93% With potassium carbonate; In acetonitrile; at 81 - 83℃; for 0.2h; (1 S)-7-nitro-2-[ 1 -(3 -ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)-ethyl]isoindolin-1-one was prepared by the following procedure. A mixture of methyl 2-bromomethyl-6-nitrobenzoate (100.0 g, 365 mmol, prepared previously in Example 6.5.2.), (iS)1 -(3 -ethoxy-4-methoxyphenyl)-2-methanesulfonylethylamine (104.7 g, 383 mmol, preparedpreviously in Example 6.5.3.), sodium hydrogen carbonate (67.5 g, 8.03 moles, from Aldrich Chemicals) and dimethyl formamide (500 mL) was charged into a 1-L 3-necked flask at room temperature under nitrogen. The reaction mixture was gradually heated to an internal temperature of 70-75C for two hours until there was less than 99% measured by HPLC based on area percentage, and a water content of <0.1% measured by Karl Fisher titration.
93% With potassium carbonate; In acetonitrile; at 81 - 83℃; for 2h;Inert atmosphere; 6.5.5. Alternative Preparation of (1S)-7-nitro-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]isoindolin-1-one (0178) (1S)-7-nitro-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl] isoindolin-1-one was also prepared by the following procedure. A mixture of methyl 2-bromomethyl-6-nitrobenzoate (100.0 g, 365 mmol, prepared previously in Example 6.5.2.), <strong>[608141-42-0](1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine</strong> (104.7 g, 383 mmol, prepared previously in Example 6.5.3.), and potassium carbonate powder (100.8 g, 730 mmol, from Aldrich Chemicals) was suspended in acetonitrile (500 mL) at room temperature. The reaction mixture was refluxed at 81-83 C. for about two hours until there was less than 2% of unreacted methyl 2-bromomethyl-6-nitrobenzoate. After the reaction mixture was cooled to 45-50 C., methanol (200 mL) was charged over 5-10 minutes. After the mixture was allowed to cool to 20-25 C. and stirred for 2 hours, deionizer water (1.40 L) was charged over 0.5-1 hour and stirred at 20-25 C. for 30 minutes and at 0-5 C. for 1-2 hours. The solid was filtered, washed with deionizer water (3×300 mL), and dried to <10% of water content as measured by Karl Fisher titration. The solid was suspended in methanol (750 mL) and refluxed for 1-1.5 hours. The suspension was cooled to 0-5 C. over 1.5-2 hours and kept at 0-5 C. for 1-1.5 hours. The solid was filtered, washed with 0-5 C. methanol (2×200 mL) and heptane (200 mL), and then dried at 40-45 C. under vacuum to a constant weight. The yield of (1S)-7-nitro-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]isoindolin-1-one was 148.0 g (93%), based on 100.0 g input of methyl 2-bromomethyl-6-nitrobenzoate. The product was found to have a purity of >99% measured by HPLC based on area percentage, and a water content of <1.0% measured by Karl Fisher titration.
93% With potassium carbonate; In acetonitrile; at 81 - 83℃; for 20h;Reflux; 10223] (1 S)-7-nitro-2-[1 -(3-ethoxy-4-methoxyphenyl)-2- (methylsulfonyl)ethyl]isoindolin-1 -one was also prepared by the following procedure. A mixture of methyl 2-bromom- ethyl-6-nitrobenzoate (100.0 g, 365 mmol, prepared previously in Example 5.7.2), (1S)-1-(3-ethoxy-4-methoxyphe- nyl)-2-methanesulfonyl-ethylamine (104.7 g, 383 mmol, prepared previously in Example 5.7.3), and potassium carbonate powder (100.8 g, 730 mmol, fromAldrich Chemicals) was suspended in acetonitrile (500 mE) at room temperature. The reaction mixture was refluxed at 81-83 C. for about two hours until there was less than 2% of unreacted methyl 2-bro- momethyl-6-nitrobenzoate. Afier the reaction mixture was cooled to 45-50 C., methanol (200 mE) was charged over 5-10 minutes. Afier the mixture was allowed to cool to 20-25 C. and stirred for 2 hours, deionized water (1.40 L) was charged over 0.5-1 hour and stirred at 20-25 C. for 30 minutes and at 0-5 C. for 1-2 hours. The solid was filtered, washed with deionized water (3 x3 00 mE), and dried to 99% measured by HPLC based on area percentage, and a water content of <1.0% measured by Karl Fisher titration
54% With triethylamine; In N,N-dimethyl-formamide; at 80 - 90℃; for 24h; Step 1 :; A solution of 2-bromomethyl-6-nitro-benzoic acid methyl ester (4.0g, 14.6 mmol), (l S)- l-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine (4.0g, 14.6 mmol) and triethylamine (4.4 mL, 31.6 mmol) in DMF (40 mL) was heated at 80C-90C for 1 day. The solvent was removed in vacuo to give an oil. The oil was extracted with ethyl acetate (150 mL) and HC1 (2N, 50 mL). The organic layer was washed with HC1 (2N, 2X50 mL), water (2X50 mL), brine (2X50 mL) and dried over MgS04. The solvent was removed in vacuo to give a yellow oil. The oil was slurried in ether (50 mL) to give a suspension. The suspension was filtered and washed with ether to give 2-[(l S)- 1 -(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-7-nitro-2,3-dihydro- isoindol- l -one as a yellow solid (3.43 g, 54% yield): lH NMR (CDC13) delta 1.5 (t, J= 7 Hz, 3H, CH3), 2.99 (s, 3Eta, CH3), 3.69 (dd, J= 5, 15 Hz, 1H, CHH), 3.86 (s, 3H, CH3), 4.07 (q, J = 7 Hz, 2H, G¾), 4.27 (dd, J = 1 1 , 15 Hz, 1H, CHH), 4.30 (d, J = 17 Hz, 1H, NCHH), 4.54 (d, J = 17 Hz, 1H, NCHH), 5.70 (dd, J = 5, 10 Hz, 1H, NCH), 6.85 (d, J= 8 Hz, 1H, Ar), 6.94-7.00 (m, 2H, Ar), 7.58- 7.76 (m, 3H, Ar).

  • 3
  • [ 608141-42-0 ]
  • [ 68-12-2 ]
  • [ 61940-21-4 ]
  • (1S)-7-nitro-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]isoindolin-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium bicarbonate; In methanol; water; A mixture of methyl 2-bromomethyl-6-nitrobenzoate (100.0 g, 365 mmol, prepared previously in Example 6.5.2.), (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethylamine (104.7 g, 383 mmol, prepared previously in Example 6.5.3.), sodium hydrogen carbonate (67.5 g, 8.03 moles, from Aldrich Chemicals) and dimethyl formamide (500 mL) was charged into a 1-L 3-necked flask at room temperature under nitrogen. The reaction mixture was gradually heated to an internal temperature of 70-75 C. for two hours until there was less than <2% of unreacted methyl 2-bromomethyl-6-nitrobenzoate. The reaction mixture was gradually heated to an internal temperature of 95-100 C. for 18 hours. The reaction mixture was cooled to 20-25 C. and transferred to an 1-L addition funnel. After purified water (1500 mL) was charged into a 5-L 3-necked flask, the reaction mixture in the addition funnel was added into water in the 5-L 3-necked flask at room temperature over 1-2 hours maintaining an internal temperature below 30 C. The reaction mixture was stirred for 2 hours at room temperature. The solid was filtered out under vacuum, washed with water (3*300 mL) and methanol (2*400 mL), and then charged into a 2-L 3-necked flask followed by methanol (1000 mL). The mixture was refluxed for 1 hour. The mixture was cooled to room temperature. The solid was collected by filtration under vacuum, washed with 200 mL methanol (2 vol), and dried to a constant weight at 40-45 C. under a vacuum at 100-120 torr. The yield of (1S)-7-nitro-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]isoindolin-1-one was 123.0 g (78%), based on 100.0 g input of methyl 2-bromomethyl-6-nitrobenzoate. The product was found to have a purity of >99% measured by HPLC based on area percentage, and a water content of <0.1% measured by Karl Fisher titration.
  • 4
  • [ 608141-42-0 ]
  • [ 61940-21-4 ]
  • cyclopropanecarboxylic acid {2-[(1S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide [ No CAS ]
 

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