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Chemical Structure| 890315-72-7 Chemical Structure| 890315-72-7

Structure of 890315-72-7

Chemical Structure| 890315-72-7

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Product Details of [ 890315-72-7 ]

CAS No. :890315-72-7
Formula : C11H12BrNO4
M.W : 302.12
SMILES Code : O=C(OC(C)(C)C)C1=CC=C(Br)C=C1[N+]([O-])=O
MDL No. :MFCD09475812
Boiling Point : No data available
InChI Key :WFQHGCOHRFRRHU-UHFFFAOYSA-N
Pubchem ID :26369829

Safety of [ 890315-72-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 890315-72-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 6
Fraction Csp3 0.36
Num. rotatable bonds 4
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 68.7
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.

2.44
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

3.69
Log Po/w (WLOGP)?

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

3.31
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.

2.44
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

1.02
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.58

Water Solubility

Log S (ESOL):?

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

-4.04
Solubility 0.0279 mg/ml ; 0.0000923 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-4.89
Solubility 0.00385 mg/ml ; 0.0000127 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

-3.52
Solubility 0.0919 mg/ml ; 0.000304 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.

-5.52 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

2.0 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)

2.5

Application In Synthesis of [ 890315-72-7 ]

* 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 [ 890315-72-7 ]

[ 890315-72-7 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 890315-72-7 ]
  • [ 63503-60-6 ]
  • [ 890316-00-4 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine)palladium (0); In ethanol; water; toluene; Referential Example 30 To 20 mL of toluene solution containing 2.0 g of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong>, 6.0 mL of ethanol, 3.0 mL of water, 1.2 g of 3-chlorophenylboronic acid, 1.7 g of sodium carbonate and 0.23 g of tetrakis(triphenylphosphine)palladium (0) were added sequentially, and the resulting mixture was heated to reflux under nitrogen atmosphere for 3 hours. Water was added after the reaction mixture was cooled to room temperature. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with a saturated sodium chloride aqueous solution, and the solvent was evaporated under reduced pressure. The obtained residue was purified with silica gel column chromatography [PSQ100B (spherical) manufactured by Fuji Silysia Chemical Ltd., eluent; hexane: ethyl acetate = 10:1] to obtain 0.70 g of tert-butyl 4-(3-chlorophenyl)-2-nitrobenzoate as white solid. 1H-NMR (DMSO-d6) delta: 1.52 (9H, s), 7.53-7.59 (2H, m), 7.77-7.82 (1H, m), 7.89-7.95 (2H, m), 8.15 (1H, dd, J = 8.1, 1.6 Hz), 8.34 (1H, d, J = 1.6 Hz).
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 3.0h;Heating / reflux; To toluene 20mL solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> 2.0g were added ethanol 6.0mL, water 3.0mL, 3-chlorophenylboronic acid 1.2g, sodium carbonate 1.7g and tetrakis(triphenylphosphine)palladium(0) 0.23g sequentially, and it was heated and refluxed under nitrogen atmosphere for 3 hours. After the reaction mixture was cooled to room temperature, water was added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after washing with saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Fuji SILYSIA Chemical Ltd., PSQ100B(spherical type), eluent; hexane:ethyl acetate=10:1] to give tert-butyl 4-(3-chlorophenyl)-2-nitrobenzoate 0.70g of white solid. 1H-NMR(DMSO-d6) delta value: 1.52(9H,s),7.53-7.59(2H,m),7.77-7.82(1H,m),7.89-7.95(2H,m),8.15(1H,dd,J=8.1,1.6Hz),8.34(1H,d,J=1.6Hz).
  • 2
  • [ 890315-72-7 ]
  • [ 98-80-6 ]
  • [ 910240-71-0 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 20℃; for 3.0h;Heating / reflux; To toluene 70mL solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> 8.8g were added phenylboronic acid 4.3g, sodium hydrogen carbonate 6.1g, ethanol 26mL, water 13mL and tetrakis(triphenylphosphine)palladium (0) 1.7g at room temperature sequentially, and it was heated and refluxed for 3 hours. After the reaction mixture was cooled to room temperature, water was added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after sequential washing with saturated sodium hydrogen carbonate aqueous solution and saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. Hexane was added to the obtained residue, solid matter was filtrated to give tert-butyl 2-nitro-4-phenylbenzoate 7.8g of white solid. 1H-NMR(DMSO-d6) delta value: 1.52(9H,s),7.47-7.56(3H,m),7.81-7.83(2H,m),7.91(1H,d,J=8.1Hz),8.11(1H,dd,J=8.1,2.0Hz),8 .27(1H,d,J=2.0Hz).
  • 3
  • [ 890315-72-7 ]
  • [ 380430-57-9 ]
  • [ 910240-97-0 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 4.5h;Heating / reflux; To toluene 24mL solution of tert-butyl 4-bromo-2-nitrobenzoate 3.0g were added ethanol 9.0mL, water 4.5mL, 4-N-(methanesulfonamide)phenylboronic acid 2.6g, sodium hydrogen carbonate 2.1g and tetrakis(triphenylphosphine)palladium(0) 0.57g, and it was heated and refluxed under nitrogen atmosphere for 4 hours and 30 minutes. After the reaction mixture was cooled to room temperature, ethyl acetate and water were added to it. After insoluble matter was filtrated, the organic layer was separated and collected, dried over anhydrous magnesium sulfate after washing with saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. Hexane and diisopropyl ether were added to the obtained residue, solid matter was filtrated to give tert-butyl 4-(4-N-(methanesulfonamido)phenyl)-2-nitrobenzoate 3.9g of white solid. 1H-NMR(DMSO-d6) delta value: 1.51(9H,s),3.06(3H,s),7.32-7.37(2H,m),7.79-7.84(2H,m),7.89(1H,d,J=8.2Hz),8.07(1H,dd,J=8.2,1.8Hz),8 .23(1H,d,J=1.8Hz),10.02-10.08(1H,broad).
  • 4
  • [ 890315-72-7 ]
  • [ 480438-74-2 ]
  • [ 910240-98-1 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 6.0h;Heating / reflux; To toluene 24mL solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> 3.0g were added ethanol 9.0mL, water 4.5mL, tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl carbonate 3.8g, sodium hydrogen carbonate 2.1g and tetrakis (triphenylphosphine)palladium(0) 0.57g sequentially, and it was heated and refluxed under nitrogen atmosphere for 6 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and water were added to it. After insoluble matter was filtrated, the organic layer was separated and collected, dried over anhydrous magnesium sulfate after washing with saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Fuji SILYSIA Chemical Ltd., PSQ100B(spherical type), eluent; hexane:ethyl acetate=3:1] to give tert-butyl 4-(3-(tert-butoxycarbonyl)oxyphenyl)-2-nitrobenzoate 3.6g of yellow oil. 1H-NMR(DMSO-d6) delta value: 1.51(9H,s),1.52(9H,s),7.2.9-7.34(1H,m),7.55-7.60(1H,m),7.70-7.76(2H,m),7.91(1H,d,J=8.0Hz),8.14(1H,dd,J=8.0,1.7Hz),8 .32(1H,d,J=1.7Hz).
  • 5
  • [ 496-15-1 ]
  • [ 890315-72-7 ]
  • [ 910240-99-2 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; XPhos;palladium diacetate; tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 20℃; for 6.5h;Heating / reflux; To toluene 30mL solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> 3.0g were added indoline 2.1mL, cesium carbonate 8.0g, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl 0.29g, tris(dibenzylideneacetone)dipalladium(0) 0.11g and palladium acetate 55mg at room temperature, and it was heated and refluxed under nitrogen atmosphere for 3 hours and 30 minutes. After the reaction mixture was cooled to room temperature, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl 0.29g, tris(dibenzylideneacetone)dipalladium(0) 0.11g and palladium acetate 55mg were added to it, and it was heated and refluxed under nitrogen atmosphere for 3 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and 10% citric acid aqueous solution were added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after washing with saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. Toluene was added to the obtained residue, dried over anhydrous magnesium sulfate after sequential washing with 1.0mol/L hydrochloric acid and saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Fuji SILYSIA Chemical Ltd., PSQ100B(spherical type), eluent; hexane:ethyl acetate=10:1] to give tert-butyl 4-(indolin-1-yl)-2-nitrobenzoate 2.0g of yellow solid. 1H-NMR(DMSO-d6) delta value: 1.48(9H,s),3.15(2H,t,J=8.4Hz),4.04(2H,t,J=8.4Hz),6.91(1 H,t,J=7.4Hz),7.17(1H,t,J=7.4Hz),7.25-7.30(1H,m),7.35(1H,d,J=8.0Hz),7.50-7.55(2H,m),7.81(1H,d,J=8.6Hz)
  • 6
  • [ 890315-72-7 ]
  • [ 67200-27-5 ]
  • [ 910241-00-8 ]
YieldReaction ConditionsOperation in experiment
With N-Methyldicyclohexylamine;palladium diacetate; In ISOPROPYLAMIDE; at 20 - 120℃; for 3.0h; To N,N-dimethylacetamide 24mL solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> 3.0g were added 2,3-dihydro-6-vinylbenzo[1,4]dioxin 2.4g, N,N-dicyclohexylmethylamine 4.0mL and palladium acetate 0.11g at room temperature, and it was stirred under nitrogen atmosphere at 120C for 3 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and water were added to it, and insoluble matter was filtrated. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after sequential washing with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Fuji SILYSIA Chemical Ltd., PSQ100B(spherical type), eluent; hexane:ethyl acetate=10:1] to give tert-butyl 4-((E)-2-(2,3-dihydrobenzo[1,4]dioxin-6-yl)vinyl)-2-nitrobenzoate 1.5g of yellow solid. 1H-NMR(DMSO-d6) delta value: 1.50(9H,s),4.27(4H,s),6.90(1H,d,J=8.3Hz),7.11-7.16(1H,m),7.17-7.20(1H,m),7.23(1H,d,J=16.5Hz),7.45(1H,d,J=16.5Hz),7.81 (1H,d,J=8.0Hz),7.89-7.93(1H,m),8.14(1H,s).
  • 7
  • [ 292638-84-7 ]
  • [ 890315-72-7 ]
  • [ 890315-79-4 ]
YieldReaction ConditionsOperation in experiment
With tetrabutylammomium bromide; sodium acetate;palladium diacetate; In N,N-dimethyl acetamide; water; ethyl acetate; Referential Example 12 To 48 mL of N,N-dimethylacetamide solution containing 6.0 g of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong>, 2.7 mL of styrene, 2.5 g of sodium acetate, 3.2 g of tetrabutylammonium bromide and 0.22 g of palladium acetate (II) were added sequentially, and heated and stirred under nitrogen atmosphere at 90C for 3 hours. After the reaction mixture was cooled to room temperature, 0.45 mL of styrene and 0.22 g of palladium acetate (II) were added and heated and stirred at 110C for 3 hours. After the reaction mixture was cooled to room temperature, water and ethyl acetate were added. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with 10% citric acid aqueous solution and a saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure. The obtained residue was purified with silica gel column chromatography [eluent; hexane:ethyl acetate = 20:1] to obtain 3.8 g of tert-butyl 2-nitro-4-((E)-2-phenylvinyl)benzoate as white solid. 1H-NMR (DMSO-d6) delta: 1.51 (9H, s), 7.32-7.45 (4H, m), 7.59 (1H, d, J = 16.6 Hz), 7.66 (2H, d, J = 7.4 Hz), 7.84 (1H, d, J = 8.1 Hz), 7.98 (1H, dd, J = 8.1, 1.5 Hz), 8.23 (1H, d, J = 1.5 Hz).
With sodium acetate;palladium diacetate; tetrabutylammomium bromide; In ISOPROPYLAMIDE; at 20 - 110℃; for 6.0h; To N,N-dimethylacetamide 48mL solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> 6.0g were added styrene 2.7mL, sodium acetate 2.5g, tetrabutylammonium bromide 3.2g and palladium acetate 0.22g sequentially, and it was heated and stirred under nitrogen atmosphere at 90C for 3 hours. After the reaction mixture was cooled to room temperature, styrene 0.45mL and palladium acetate 0.22g were added to it, and it was stirred at 110C for 3 hours. After the reaction mixture was cooled to room temperature, water and ethyl acetate were added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after sequential washing with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [eluent; hexane:ethyl acetate=20:1] to give tert-butyl 2-nitro-4-((E)-2-phenylvinyl)benzoate 3.8g of white solid. 1H-NMR(DMSO-d6) delta value: 1.51(9H,s),7.33-7.45(4H,m),7.59(1H,d,J=16.6Hz),7.66(2H,d,J=7.4Hz), 7.84(1H,d,J=8.1Hz),7.98(1H,dd,J=8.1,1.5Hz),8.23(1H,d,J= 1.5Hz).
  • 8
  • [ 507-19-7 ]
  • [ 99277-71-1 ]
  • [ 890315-72-7 ]
YieldReaction ConditionsOperation in experiment
With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate; In methanol; N,N-dimethyl acetamide; water; ethyl acetate; Referential Example 2 To 50 mL of N,N-dimethylacetamide solution containing 5.0 g of 4-bromo-2-nitrobenzoic acid, 41 g of potassium carbonate, 4.6 g of benzyltriethylammonium chloride and 69 mL of 2-bromo-2-methylpropane were added at room temperature and stirred at 55C for 10 hours. After the reaction mixture was cooled to room temperature, 12 mL of 2-bromo-2-methylpropane was added and stirred at 55C for 4 hours. After the reaction mixture was cooled to room temperature, water and ethyl acetate were added. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with 10% citric acid aqueous solution and a saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure. Methanol was added to the obtained residue and solid substances were separated by filtration to obtain 3.0 g of tert-butyl 4-bromo-2-nitrobenzoate as white solid. 1H-NMR (CDCl3) delta: 1.55 (9H, s), 7.63 (1H, d, J = 8.3 Hz), 7.77 (1H, dd, J = 8.3, 1.9 Hz), 7.95 (1H, d, J = 1.9 Hz).
With potassium carbonate;N-benzyl-N,N,N-triethylammonium chloride; In ISOPROPYLAMIDE; at 20 - 55℃; for 14.0h; To N,N-dimethylacetamide 50mL solution of 4-bromo-2-nitrobenzoic acid 5.0g were added potassium carbonate 41g, benzyltriethylammonium chloride 4.6g and 2-bromo-2-methylpropane 69mL at room temperature and it was stirred at 55C for 10 hours. After the reaction mixture was cooled to room temperature, 2-bromo-2-methylpropane 12mL was added to it, and it was stirred at 55C for 4 hours. After the reaction mixture was cooled to room temperature, water and ethyl acetate were added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after sequential washing with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. Methanol was added to the obtained residue, solid matter was filtrated to give tert-butyl 4-bromo-2-nitrobenzoate 3.0g of white solid. 1H-NMR(CDCl3) delta value: 1.55(9H,s),7.63(1H,d,J=8.3Hz),7.77(1H,dd,J=8.3,1.9Hz),7 .95(1H,d,J=1.9Hz).
  • 9
  • [ 300-57-2 ]
  • [ 890315-72-7 ]
  • [ 890315-81-8 ]
  • 10
  • [ 626-20-0 ]
  • [ 890315-72-7 ]
  • [ 890316-10-6 ]
YieldReaction ConditionsOperation in experiment
With triethylamine;palladium diacetate; In N,N-dimethyl acetamide; water; ethyl acetate; Referential Example 40 To 5 mL of N,N-dimethylacetamide solution containing 0.50 g of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong>, 0.37 mL of 3-vinylanisole, 0.47 mL of triethylamine and 0.11 g of palladium acetate were added at room temperature and stirred under nitrogen atmosphere at 110C for 4 hours. Ethyl acetate and water were added after the reaction mixture was cooled to room temperature. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with 10% citric acid aqueous solution and a saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure. The obtained residue was purified with silica gel column chromatography [PSQ100B (spherical) manufactured by Fuji Silysia Chemical Ltd., eluent; hexane: ethyl acetate = 10:1] to obtain 0.20 g of tert-butyl 4-((E)-2-(3-methoxyphenyl)vinyl)-2-nitrobenzoate a pale yellow solid. 1H-NMR (DMSO-d6) delta: 1.51 (9H, s), 3.81 (3H, s), 6.90-6.94 (1H, m), 7.20-7.27 (2H, m), 7.34 (1H, t, J = 7.9 Hz), 7.43 (1H, d, J = 16.6 Hz), 7.55 (1H, d, J = 16.6 Hz), 7.84 (1H, d, J = 8.0 Hz), 7.97 (1H, d, J = 7.8 Hz), 8.21 (1H, s).
With triethylamine;palladium diacetate; In ISOPROPYLAMIDE; at 20 - 110℃; for 4.0h; To N,N-dimethylacetamide 5mL solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> 0.50g were added 3-vinylanisole 0.37mL, triethylamine 0.47mL and palladium acetate 0.11g at room temperature, and it was stirred under nitrogen atmosphere at 110C for 4 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and water were added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after sequential washing with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Fuji SILYSIA Chemical Ltd., PSQ100B(spherical type), eluent; hexane:ethyl acetate=10:1] to give tert-butyl 4-((E)-2-(3-methoxyphenyl)vinyl)-2-nitrobenzoate 0.20g of pale yellow solid. 1H-NMR(DMSO-d6) delta value: 1.51(9H,s),3.81(3H,s),6.90-6.94(1H,m),7.20-7.27(2H,m),7.34(1H,t,J=7.9Hz),7.43(1H,d,J=16.6Hz),7.55( 1H,d,J=16.6Hz),7.84(1H,d,J=8.0Hz),7.97(1H,d,J=7.8Hz),8. 21(1H,s).
  • 11
  • [ 890315-72-7 ]
  • [ 890315-73-8 ]
YieldReaction ConditionsOperation in experiment
Iron powder 3.0g were added to a mixed solution methanol 28mL and acetic acid 28mL of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> 5.5g, it was heated and refluxed for 1 hour. After the reaction mixture was cooled to room temperature, saturated sodium hydrogen carbonate aqueous solution and ethyl acetate were added to it, and insoluble matter was filtrated. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after sequential washing with saturated sodium hydrogen carbonate aqueous solution and saturated sodium chloride aqueous solution, the solvent was removed under reduced pressure to give tert-butyl 2-amino-4-bromobenzoate 4.3g of pale yellow oil. 1H-NMR-(DMSO-d6) delta value: 1.52(9H,s),6.65(1H,dd,J=8.5,2.0Hz),6.78(2H,s),6.98(1H,d ,J=2.0Hz),7.55(1H,d,J=8.5Hz).
  • 12
  • [ 890315-72-7 ]
  • [ 768-56-9 ]
  • [ 890315-83-0 ]
  • 13
  • [ 300-57-2 ]
  • [ 890315-72-7 ]
  • [ 6163-58-2 ]
  • tert-butyl 2-nitro-4-(3-phenyl-1-propenyl)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine;palladium diacetate; In toluene; Referential Example 14 19 mg of palladium acetate (II) was added to 5 mL of toluene solution containing 0.50 g of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong>, 50 mg of tri(o-tolyl)phosphine, 0.44 mL of allylbenzene and 0.46 mL of triethylamine, and the resulting mixture was heated to reflux under nitrogen atmosphere for 2 hours. After the reaction mixture was cooled to room temperature, 20 mg of palladium acetate (II) was added and the resulting mixture was heated to reflux for 7 hours. After the reaction mixture was cooled to room temperature, insoluble were removed by filtration, and the solvent was evaporated under reduced pressure. The obtained residue was purified with silica gel column chromatography [eluent; hexane:ethyl acetate = 30:1] to obtain 0.31 g of tert-butyl 2-nitro-4-(3-phenyl-1-propenyl)benzoate.
  • 14
  • [ 890315-72-7 ]
  • [ 768-56-9 ]
  • [ 6163-58-2 ]
  • tert-butyl 2-nitro-4-(4-phenyl-1-butenyl)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine;palladium diacetate; In toluene; Referential Example 15 19 mg of palladium acetate (II) was added to 5 mL of toluene solution containing 0.50 g of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong>, 50 mg of tri(o-tolyl)phosphine, 0.50 mL of 4-phenyl-1-butene and 0.46 mL of triethylamine, and the resulting mixture was heated to reflux under nitrogen atmosphere for 4 hours and 30 minutes. After the reaction mixture was cooled to room temperature, 20 mg of palladium acetate (II) was added and the resulting mixture was heated to reflux for 5 hours and 30 minutes. After cooled to room temperature, the reaction mixture was purified with silica gel column chromatography [eluent; hexane:ethyl acetate = 30:1] to obtain 0.35 g of tert-butyl 2-nitro-4-(4-phenyl-1-butenyl)benzoate.
  • 15
  • [ 890315-72-7 ]
  • [ 7439-89-6 ]
  • [ 890315-73-8 ]
YieldReaction ConditionsOperation in experiment
With sodium bicarbonate; acetic acid; In methanol; ethyl acetate; Referential Example 4 3.0 g of iron powder was added to a mixed solution of 28 mL of methanol and 28 mL of acetic acid containing 5.5 g of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong>, and the resulting mixture was heated to reflux for 1 hour. After the reaction mixture was cooled to room temperature, a saturated sodium hydrogen carbonate aqueous solution and ethyl acetate were added and insoluble were removed by filtration. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with a saturated sodium hydrogen carbonate aqueous solution and a saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure to obtain 4.3 g of tert-butyl 2-amino-4-bromobenzoate as pale yellow oil. 1H-NMR (DMSO-d6) delta: 1.52 (9H, s), 6.65 (1H, dd, J = 8.5, 2.0 Hz), 6.78 (2H, s), 6.98 (1H, d, J = 2.0 Hz), 7.55 (1H, d, J = 8.5 Hz).
  • 16
  • [ 890315-72-7 ]
  • [ 34381-71-0 ]
  • [ 1108745-46-5 ]
YieldReaction ConditionsOperation in experiment
41% With caesium carbonate;racemic-2-(di-tert-butylphosphino)-1,1?-binaphthyl; bis(dibenzylideneacetone)-palladium(0); In toluene; at 100℃; for 18.0h; Example 8Preparation of tert-buty 4-[(2S)-l-methylpyrrolidin-2-yl]methoxy}-2- nitrobenzoate; In a round bottomed three neck flask under argon atmosphere were added toluene (15 ml), CSCO3 (1.6 gr, 5 mmol ), phosphine ligand 2-(di-tert-butylphosphino)-l,l'- binaphthyl (331 mg, 0.83 mmol) and Pd(dba)2 (380 mgr, 0.66 mmol). The mixture was degassed bubbling argon for five minutes. Then <strong>[890315-72-7]4-bromo-2-nitrobenzoic acid tert butyl ester</strong> (1 gr, 3.31 mmol) and (S)-(-)-l-methyl-2-pyrrolidinemethanol (0.78 ml, 6.62 mmol) were added and the mixture was heated to 100 0C for 18 hr. The reaction was cooled to room temperature, quenched with 30 ml of water and extracted twice with 25 ml of AcOEt. The organic phases were collected, dried over Na2SO4 and the solvents evaporated to obtain a red oil which was subjected to chromatography purification on a Biotage SPl automated system (90:10 DCM/MeOH (isocratic) to yield the pure title compound as a yellowish oil (460 mgr, 1.36 mmol, 41% yield)ESI(+) MS: m/z 337 (MH+).
  • 17
  • [ 890315-72-7 ]
  • [ 380430-68-2 ]
  • [ 1237518-52-3 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 2.0h;Inert atmosphere; Reflux; Reference Example 2b; Water (0.6 mL), sodium carbonate (0.16 g), 3-(tert-butoxycarbonylamino)phenylboronic acid (0.14 g), and tetrakis(triphenylphosphine)palladium(0) (29 mg) were added to an ethylene glycol dimethyl ether (2.0 mL) solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> (0.15 g), followed by heating to reflux under a nitrogen atmosphere for 2 hours. The reaction mixture was cooled to room temperature, and then ethyl acetate and a saturated aqueous solution of sodium bicarbonate were added thereto. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 95-91% hexane/ethyl acetate] to obtain 0.17 g of tert-butyl 4-(3-(tert-butoxycarbonylamino)phenyl)-2-nitrobenzoate as a light yellow solid.1H-NMR (CDCl3) delta: 1.54 (9H, s), 1.58 (9H, s), 6.55-6.63 (1H, broad), 7.24-7.28 (1H, m), 7.33 (1H, d, J=8.6 Hz), 7.39 (1H, d, J=7.8 Hz), 7.74 (1H, s), 7.80 (1H, d, J=8.1 Hz), 7.84 (1H, dd, J=7.9, 1.6 Hz), 7.99 (1H, d, J=1.7 Hz).
  • 18
  • [ 890315-72-7 ]
  • [ 159624-15-4 ]
  • [ 1237518-14-7 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 2.5h;Reflux; Inert atmosphere; Reference Example 36a; Water (0.6 mL), sodium carbonate (0.16 g), tert-butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (0.19 g), and tetrakis(triphenylphosphine)palladium(0) (29 mg) were added to an ethylene glycol dimethyl ether (2.0 mL) solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> (0.15 g), followed by heating to reflux under a nitrogen atmosphere for 2 hours and 30 minutes. The reaction mixture was cooled to room temperature, and then ethyl acetate and a 10% aqueous solution of citric acid were added thereto. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 91-80% hexane/ethyl acetate] to obtain 0.21 g of tert-butyl 4-(2-(tert-butoxycarbonylamino)phenyl)-2-nitrobenzoate as a yellow solid.1H-NMR (CDCl3) delta: 1.46 (9H, s), 1.60 (9H, s), 6.14-6.22 (1H, broad), 7.16-7.23 (2H, m), 7.38-7.45 (1H, m), 7.67 (1H, dd, J=8.1, 1.7 Hz), 7.84 (1H, d, J=8.1 Hz), 7.85 (1H, d, J=1.7 Hz), 7.96 (1H, d, J=8.5 Hz).
  • 19
  • [ 890315-72-7 ]
  • [ 1237518-20-5 ]
  • 20
  • [ 890315-72-7 ]
  • [ 1237518-22-7 ]
  • 21
  • [ 890315-72-7 ]
  • [ 1237518-60-3 ]
  • 22
  • [ 890315-72-7 ]
  • [ 1237518-61-4 ]
  • 23
  • [ 890315-72-7 ]
  • [ 685103-98-4 ]
  • [ 1237518-51-2 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; for 2.0h;Inert atmosphere; Reflux; Reference Example 1b; Water (15 mL), sodium carbonate (4.6 g), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinoline (5.1 g), and bis(triphenylphosphine)palladium(II) dichloride (0.24 g) were added to an ethylene glycol dimethyl ether (50 mL) solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> (5.0 g), followed by heating to reflux under a nitrogen atmosphere for 2 hours. The reaction mixture was cooled to room temperature, and then ethyl acetate and water were added thereto. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 85-75% hexane/ethyl acetate] to obtain 5.8 g of tert-butyl 4-(isoquinolin-4-yl)-2-nitrobenzoate as a brown oily substance.1H-NMR (DMSO-d6) delta: 1.55 (9H, s), 7.76-7.83 (1H, m), 7.83-7.88 (2H, m), 7.99-8.02 (2H, m), 8.21 (1H, s), 8.28 (1H, d, J=8.0 Hz), 8.55 (1H, s), 9.44 (1H, s).
  • 24
  • [ 288-13-1 ]
  • [ 890315-72-7 ]
  • [ 1237518-59-0 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;copper(l) iodide; D-Prolin; In dimethyl sulfoxide; at 100℃; for 3.0h;Inert atmosphere; Reference Example 11b; 1H-Pyrazole (0.14 g), potassium carbonate (0.46 g), D-proline (38 mg), and copper(I) iodide (32 mg) were added to a dimethyl sulfoxide (5 mL) solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> (0.50 g), followed by stirring under a nitrogen atmosphere at 100 C. for 3 hours. After cooling the reaction mixture to room temperature, ethyl acetate and water were added thereto, and the insoluble substance was removed by filtration. The organic layer was separated, washed with water and a saturated aqueous solution of sodium chloride sequentially, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [Fuji Silysia Chemical Ltd., PSQ100B (spherical), eluent: 100-80% hexane/ethyl acetate] to obtain 0.20 g of tert-butyl 2-nitro-4-(1H-pyrazol-1-yl)benzoate as a white solid.1H-NMR (CDCl3) delta: 1.57 (9H, s), 6.56 (1H, dd, J=2.6, 1.8 Hz), 7.79 (1H, d, J=1.8 Hz), 7.88 (1H, d, J=8.5 Hz), 7.95 (1H, dd, J=8.5, 2.1 Hz), 8.01 (1H, d, J=2.6 Hz), 8.15 (1H, d, J=2.1 Hz).
  • 25
  • [ 890315-72-7 ]
  • [ 73183-34-3 ]
  • [ 1237518-55-6 ]
YieldReaction ConditionsOperation in experiment
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 95 - 100℃; for 2.0h;Inert atmosphere; Reference Example 7b; Potassium acetate (2.0 g), bis(pinacolato)diboron (3.4 g), and (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride methylene chloride complex (0.27 g) were added to a dioxane (20 mL) solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> (2.0 g), followed by stirring under a nitrogen atmosphere at 95 to 100 C. for 2 hours. After cooling the reaction mixture to room temperature, the insoluble substance was removed by filtration, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 80% hexane/ethyl acetate] and then purified by silica gel column chromatography [eluent: 95-90% hexane/ethyl acetate] to obtain 2.0 g of tert-butyl 2-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate as a white solid.1H-NMR (CDCl3) delta: 1.26 (12H, s), 1.36 (9H, s), 7.69 (1H, d, J=7.6 Hz), 7.99-8.06 (1H, m), 8.23-8.27 (1H, m).
  • 26
  • [ 890315-72-7 ]
  • [ 5720-06-9 ]
  • [ 1237518-13-6 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; for 2.5h;Reflux; Inert atmosphere; Reference Example 35a; Water (9.0 mL), sodium carbonate (2.6 g), 2-methoxyphenylboronic acid (1.8 g), and bis(triphenylphosphine)palladium(II) dichloride (0.14 g) were added to an ethylene glycol dimethyl ether (30 mL) solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> (3.0 g), followed by heating to reflux under a nitrogen atmosphere for 2 hours and 30 minutes. The reaction mixture was cooled to room temperature, and then a 10% aqueous solution of citric acid and ethyl acetate were added thereto. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 99-91% hexane/ethyl acetate] to obtain 3.3 g of tert-butyl 4-(2-methoxyphenyl)-2-nitrobenzoate as a light yellow oily substance.1H-NMR (CDCl3) delta: 1.58 (9H, s), 3.83 (3H, s), 6.99-7.04 (1H, m), 7.04-7.10 (1H, m), 7.32 (1H, dd, J=7.6, 1.7 Hz), 7.40 (1H, ddd, J=8.3, 7.6, 1.7 Hz), 7.73-7.77 (1H, m), 7.78 (1H, dd, J=7.9, 1.6 Hz), 8.01 (1H, d, J=1.0 Hz).
  • 27
  • [ 890315-72-7 ]
  • [ 1237518-21-6 ]
  • 28
  • [ 890315-72-7 ]
  • [ 1237518-57-8 ]
  • 29
  • [ 890315-72-7 ]
  • [ 1237518-83-0 ]
  • 30
  • [ 890315-72-7 ]
  • [ 1237518-84-1 ]
  • 31
  • [ 890315-72-7 ]
  • [ 1237519-19-5 ]
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  • [ 890315-72-7 ]
  • [ 1237519-20-8 ]
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  • [ 890315-72-7 ]
  • [ 1237519-21-9 ]
  • 34
  • [ 890315-72-7 ]
  • [ 1237514-72-5 ]
  • 35
  • [ 890315-72-7 ]
  • [ 1237519-22-0 ]
 

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