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Chemical Structure| 5763-61-1 Chemical Structure| 5763-61-1

Structure of 5763-61-1

Chemical Structure| 5763-61-1

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Product Details of [ 5763-61-1 ]

CAS No. :5763-61-1
Formula : C9H13NO2
M.W : 167.21
SMILES Code : NCC1=CC=C(OC)C(OC)=C1
MDL No. :MFCD00008116
InChI Key :DIVNUTGTTIRPQA-UHFFFAOYSA-N
Pubchem ID :79832

Safety of [ 5763-61-1 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P260-P264-P280-P301+P330+P331+P310-P303+P361+P353+P310+P363-P304+P340+P310-P305+P351+P338+P310-P405-P501
Class:8
UN#:2735
Packing Group:

Computational Chemistry of [ 5763-61-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 47.1
TPSA ?

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

44.48 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.88
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

0.35
Log Po/w (WLOGP)?

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

1.01
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.

0.92
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

1.44
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.12

Water Solubility

Log S (ESOL):?

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

-1.27
Solubility 9.0 mg/ml ; 0.0538 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.

-0.85
Solubility 23.7 mg/ml ; 0.142 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

-2.69
Solubility 0.341 mg/ml ; 0.00204 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.

-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

1.0
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

0.0 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)

1.22

Application In Synthesis of [ 5763-61-1 ]

* 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 [ 5763-61-1 ]

[ 5763-61-1 ] Synthesis Path-Downstream   1~17

  • 2
  • [ 6272-25-9 ]
  • [ 5763-61-1 ]
  • (3,4-Dimethoxy-benzyl)-(6-nitro-quinoxalin-2-yl)-amine [ No CAS ]
  • 3
  • [ 2106-50-5 ]
  • [ 5763-61-1 ]
  • [ 1026026-68-5 ]
  • 4
  • [ 132794-07-1 ]
  • [ 5763-61-1 ]
  • [ 247568-34-9 ]
  • [ 247570-13-4 ]
YieldReaction ConditionsOperation in experiment
PREPARATION 151 4-Chloro-2,5-difluoro-N-(3,4-dimethoxybenzyl)benzamide (1.66 g) was obtained from <strong>[132794-07-1]4-chloro-2,5-difluorobenzoic acid</strong> (1.05 g) and veratrylamine (0.91 mL) in a in a manner similar to preparation 1. NMR (DMSO-d6, delta): 3.73 (3H, s), 3.74 (3H, s), 4.39 (2H, d, J=6 Hz), 6.81-6.97 (3H, m), 7.67 (1H, dd, J=6, 9 Hz), 7.79 (1H, dd, J=6, 9 Hz), 8.96 (1H, t, J=6 Hz).
  • 5
  • [ 76872-23-6 ]
  • [ 5763-61-1 ]
  • 2-chloro-6-methyl-4-(3,4-dimethoxybenzylamino)-thieno-[2,3-d]-pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 23 Following the procedure of Example 1, the reaction of 3,4-dimethoxybenzylamine with 2,4-dichloro-6-methyl-thieno-[2,3-d]-pyrimidine yields 2-chloro-6-methyl-4-(3,4-dimethoxybenzylamino)-thieno-[2,3-d]-pyrimidine.
  • 6
  • [ 5926-51-2 ]
  • [ 5763-61-1 ]
  • [ 909397-79-1 ]
YieldReaction ConditionsOperation in experiment
79% With acetic acid; at 80℃; for 3h; General procedure: 3-Bromomaleic anhydride (1.0 equiv, 5.65 mmol, 1.0 g) wasdissolved in AcOH (20 mL). Methylamine hydrochloride(1.0 equiv, 5.65 mmol, 0.37 g) was then added, and thereaction was heated at 80 °C for 3 h. Solvent was removed invacuo, and the crude mixture was purified by columnchromatography over silica gel (EtOAc?hexane 0?30percent)using an ISCOTM purification system to afford 0.97 g of awhite solid (90percent yield).
67% Example XI Preparation of l-Aryl-3-aza-bicyclo[3.1.0]hexane hydrochlorides Using Reaction Scheme 17 A. Synthesis of 3-Bromo-l-(3.4-dimethoxybenzyl)maleimide A solution of <strong>[5926-51-2]bromomaleic anhydride</strong> (Aldrich, 20.0 g, 0.113 mole) in anhydrous tetrahydrofuran (100 mL) under nitrogen was treated dropwise with a solution of 3,4-dimethoxybenzylamine (20.0 g, 0.1196 mole) in anhydrous THF (40 mL) over 30 min, and the stirred mixture was then refluxed for 3 h and maintained at room temperature for 20 h. The mixture was concentrated in vacuo, suspended in acetic anhydride (135 mL), treated with anhydrous sodium acetate (6.15 g, 75 mmol), and heated to 5O0C with stirring under nitrogen for 4 h (solids dissolved after a few minutes). The mixture was concentrated in vacuo and dissolved in methylene chloride (300 mL). The solution was washed with saturated aqueous sodium bicarbonate (150 mL), then with water (150 mL), dried (Na2SO4), and concentrated in vacuo to a brown residue. This was dissolved in methylene chloride and passed through a column of silica gel (~400 mL EPO <DP n="124"/>volume) and eluted with methylene chloride to afford a tan solid, which was recrystallized from ethyl acetate/heptane (2 crops) to afford 3-bromo-l-(3,4- dimethoxybenzyl)maleimide (24.75 g, 67percent) as a pale tan solid. NO MS (M+l) peak. 1H NMR (CDCl3) delta 6.89-6.94 (m, 2H), 6.84 (s, IH), 6.78 (d, IH, J=8Hz), 4.63 (s, 2H), 3.86 (s, 3H), 3.84 (s, 3H).
67% Example XII Preparation of l-(4-Trifluoromethoxyphenyl)-3-azabicvclo[3.1 ,0]hexane, hydrochlorideUsinfi Reaction Scheme 17A. Synthesis of 3-Bromo-l-(3,4-dimethoxybenzyl)maIeimide EPO <DP n="104"/>A solution of <strong>[5926-51-2]bromomaleic anhydride</strong> (Aldrich, 20.0 g, 0.113 mole) in anhydrous tetrahydrofuran (100 mL) under nitrogen was treated dropwise with a solution of 3,4-dimethoxybenzylamine (20.0 g, 0.1196 mole) in anhydrous THF (40 mL) over 30 min, then the stirred mixture was refluxed for 3 h and maintained at room temperature for 20 h. The mixture was concentrated in vacuo, suspended in acetic anhydride (135 mL), treated with anhydrous sodium acetate (6.15 g, 75 mmol), and heated to 5O0C with stirring under nitrogen for 4 h (solids dissolved after a few minutes). The mixture was concentrated in vacuo and dissolved in methylene chloride (300 mL). The solution was washed with saturated aqueous sodium bicarbonate (150 mL), then with water (150 mL), dried (Na2SO4), and concentrated in vacuo to a brown residue. This was dissolved in methylene chloride and passed through a column of silica gel (-400 mL volume) and eluted with methylene chloride to afford a tan solid, which was recrystallized from ethyl acetate/heptane (2 crops) to afford 3-bromo-l-(3,4-dimethoxybenzyl)maleimide (24.75 g, 67percent) as a pale tan solid. NO MS (M+l) peak. 1H NMR (CDCl3) delta 6.89-6.94 (m, 2H), 6.84 (s, IH), 6.78 (d, IH, J=8Hz), 4.63 (s, 2H), 3.86 (s, 3H), 3.84 (s, 3H).
  • 7
  • [ 1071017-49-6 ]
  • [ 5763-61-1 ]
  • (3,4-dimethoxybenzyl)-(7-pyridin-4-ylisoquinolin-5-yl)amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% In 1-methyl-pyrrolidin-2-one; at 100℃; for 16h; (3,4-Dimethyloxy-benzyl)-(3-pyridin-4-yl-[2,6]naphthyridin-1-yl)-amine; <n="42"/>To a solution of 1-chloro-3-pyridin-4-yl-[2,6]naphthyridine (446.6 mg, 1.84 mmol) in 1-Methyl- pyrrolidin-2-one (8 ml_) is added 3,4-Dimethoxy-benzylamine (0.835 ml_, 5.54 mmol). The reaction mixture is heated to 1000C for 16 h, cooled to rt, the insoluble impurities are filtered and the filtrate concentrated under vacuum. Methanol is added and the formed precipitated filtered and dried under vacuum to yield to the title compound as a yellow solid (597 mg, 1.6 mmol, 87%), which is used without further purification for the next step. MS: 373.1 [M+1]+
  • 8
  • (+/-)-cis-4-methyl-1-(phenylmethyl)-piperidin-3-ylamine [ No CAS ]
  • [ 5763-61-1 ]
  • [ 154012-15-4 ]
  • ethyl rac-4-[(3R,4R)-1-benzyl-4-methylpiperidin-3-yl]amino}-6-[(3,4-dimethoxybenzyl)amino]-5-nitronicotinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Preparation 31 To a solution of <strong>[154012-15-4]ethyl 4,6-dichloro-5-nitronicotinate</strong> (500 mg) in NMP (1 mL) were added DIPEA (0.328 mL) and a racemic mixture of (3R,4R)-1-benzyl-4-methylpiperidine-3-amine and (3S,4S)-1-benzyl-4-methylpiperidine-3-amine (385 mg). The reaction mixture was stirred at ambient temperature for 1 hour. To the reaction mixture were added DIPEA (0.328 mL) and 1-(3,4-dimethoxyphenyl)methaneamine (315 mg). The reaction mixture was stirred at 110C for 2 hours. The mixture was extracted with EtOAc and washed with water. The organic layer was dried over anhydrous MgSO4 and filtered. The filtrate was evaporated in vacuo. The residue was purified by silica gel column chromatography (EtOAc:n-hexane = 1:2) to afford a mixture (670 mg) of ethyl 4-[(3R,4R)-1-benzyl-4-methylpiperidine-3-yl]-amino}-6-[(3,4-dimethoxybenzyl)amino]-5-nitronicotinate and ethyl 4-[(3S,4S)-1-benzyl-4-methylpiperidine-3-yl]amino}-6-[(3,4-dimethoxybenzyl)amino]-5-nitroniootinate as a yellow amorphous solid.
Preparation Example 16 To a mixed liquid of <strong>[154012-15-4]4,6-dichloro-5-nitronicotinic acid ethyl ester</strong> (5.7 g) in DMF (40 mL) were added rac-(3R,4R)-1-benzyl-4-methylpiperidin-3-amine (4.39 g) and N,N-diisopropylethylamine (3.7 mL), followed by stirring at room temperature for 1 hour. To the reaction mixture were added 1-(3,4-dimethoxyphenyl)methaneamine (4.8 mL) and N,N-diisopropylethylamine (9.4 mL), followed by stirring at 110 C. for 2 hours. The reaction mixture was quenched with water, and then the mixture was extracted with EtOAc and washed with water. The organic layer was dried over MgSO4 and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc/Hx=1/4 to 1/2) to obtain ethyl rac-4-[(3R,4R)-1-benzyl-4-methylpiperidin-3-yl]amino}-6-[(3,4-dimethoxybenzyl)amino]-5-nitronicotinate (9.9 g) as a yellow amorphous substance.
Preparation Example 16; To a mixed liquid of <strong>[154012-15-4]4,6-dichloro-5-nitronicotinic acid ethyl ester</strong> (5.7 g) in DMF (40 mL) were added rac-(3R,4R)-1-benzyl-4-methylpiperidin-3-amine (4.39 g) and N,N-diisopropylethylamine (3.7 mL), followed by stirring at room temperature for 1 hour. To the reaction mixture were added 1-(3,4-dimethoxyphenyl)methaneamine (4.8 mL) and N,N-diisopropylethylamine (9.4 mL), followed by stirring at 110C for 2 hours. The reaction mixture was quenched with water, and then the mixture was extracted with EtOAc and washed with water. The organic layer was dried over MgSO4 and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc/Hx = 1/4 to 1/2) to obtain ethyl rac-4-[(3R,4R)-1-benzyl-4-methylpiperidin-3-yl]amino}-6-[(3,4-dimethoxybenzyl)amino]-5-nitronicotinate (9.9 g) as a yellow amorphous substance.
  • 9
  • [ 149057-19-2 ]
  • [ 5763-61-1 ]
  • [ 1311150-55-6 ]
  • 10
  • [ 5763-61-1 ]
  • [ 1204-06-4 ]
  • [ 1508307-04-7 ]
YieldReaction ConditionsOperation in experiment
81% General procedure: The round-bottom flask was charged with trans-Indole-3-acrylic acid (1.0 equiv.) or 3-Indolepropionic acid (1.0 equiv.) and the resulting mixture of DMF in CH2Cl2 (v:v, 1:3). DIPEA (1.5 equiv.) followed by HBTU (1.5 equiv.) were added to the solution. After stirring at room temperature for 30 min, amine (1.0 equiv.) was added and stirred overnight at RT. The excess solvent was evaporated and then diluted with water and EtOAc, and the two layers were separated. The aqueous solution was extracted with EtOAc. The combined organic solution was washed with water and brine, dried over magnesium sulfate, and filtered. The residue was purified by column chromatography on silica gel using 0-60% EtOAc in Hexanes as eluant to give the desired products 2a-2f.
68% General procedure: To a solution of the acid derivative (1mmol) in CH2Cl2 were added triethylamine (2mmol) and ethyl chloroformate (1mmol), followed by stirring at 0C for 30min. After addition of the appropriate amine derivative (1.2mmol), the mixture was stirred for an additional 1h at 0C. Then, the reaction mixture was warmed to room temperature and stirred overnight. After the solvent was evaporated under reduced pressure, acetone was added, filtered, and evaporated. The residue was dissolved in CH2Cl2, and the organic phase was washed with a 1% NaHCO3 solution and brine, dried over Na2SO4, and evaporated under vacuum. The final residue was purified by flash column chromatography (Combiflash Rf) using CH2Cl2-MeOH (0-5%) as eluents. 4.3.11 (E)-N-(3,4-Dimethoxybenzyl)-3-(1H-indol-3-yl)acrylamide 3k 47 Yield 68%, mp 176-178 C; IR (FTIR/FTNIR-ATR): 1657 cm-1 (C=O), 3292 cm-1 (N-H). 1H NMR (DMSO-d6) delta: 11.52 (1H, s), 8.24 (1H, t, J = 5.6 Hz), 7.86 (1H, d, J = 7.6 Hz), 7.72 (1H, s), 7.61 (1H, d, J = 16 Hz), 7.42 (1H, d, J = 7.6 Hz), 7.13 (2H, m), 6.89 (2H, m), 6.80 (1H, m), 6.64 (1H, d, J = 16 Hz), 4.30 (2H, d, J = 5.2 Hz), 3.71 (3H, s), 3.69 (3H, s). 13C NMR (DMSO-d6) delta: 166.8, 149.2, 148.4, 138.0, 133.9, 132.7, 131.0, 125.5, 122.8, 120.9, 120.6, 120.2, 116.8, 112.9, 112.7, 112.3, 112.1, 56.2, 56.0, 42.8; HRMS C20H21N2O3 [M+H]+ Calcd 337.1552, Found m/z 337.1544.
  • 11
  • [ 31739-56-7 ]
  • [ 590-93-2 ]
  • [ 119072-55-8 ]
  • [ 5763-61-1 ]
  • [ 1604835-46-2 ]
  • 12
  • [ 57595-23-0 ]
  • [ 5763-61-1 ]
  • methyl 4-((3,4-dimethoxybenzyl)amino)-2,5-dihydrofuran-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
In ethanol; at 90℃; for 1.5h; To a solution of (3 ,4-dimethoxyphenyl)methanamine (212 g, 1.27 mol) in anhydrous ethanol (1.1 L) was added dropwise the solution of crude 11 (300 g, assay 55% 1.15 mol) in anhydrous ethanol (1.1 L) over 30 mm using an addition funnel at 90 C (note: slow addition is crucial to good yield). The reaction was subsequently aged at 90 C for 1 h. After the reaction was complete shown by LCMS, the reaction was cooled to ambient temperature and concentrated. The crude residual was purified by trituation with methanol (5 V) to give methyl5 4-((3 ,4-dimethoxybenzyl)amino)-2,5-dihydrofuran-3 -carboxylate (14) as a solid. ?H NMR (CDC13, 400 MHz) : 7.08 (m, 1H), 6.46 (m, 2H), 4.76 (m, 4H), 4.19 (m, 2H), 3.81 (s, 3H), 3.81 (s, 3H), 3.69 (s, 3H), 2.69 (t, 1H). LC/MS (m/z): 294 (M+H).
In ethanol; at 90℃; for 1.5h; Step B. Methyl 4- ( (3, 4-dimethoxybenzyl) amino) -2, 5-dihydrofuran-3-carboxylate (12)[0227][0228]To a solutio n of (3, 4-dimethoxyphenyl) methanamine (212 g, 1.27 mol) in anhydrous ethanol (1.1 L) was added dropwise the solution of crude 11 (300 g, assay 55 1.15 mol) in anhydrous ethanol (1.1 L) over 30 min using an addition funnel at 90 (note: slow addition is crucial to good yield) . The reaction was subsequently aged at 90 for 1 h. After the reaction was complete shown by LCMS, the reaction was cooled to ambient temperature and concentrated. The crude residual was purified by trituation with methanol (5 V) to give methyl 4- ( (3, 4-dimethoxybenzyl) amino) -2, 5-dihydrofuran-3-carboxylate (12) as a solid.1H NMR (CDCl3, 400 MHz) delta: 7.08 (m, 1H) , 6.46 (m, 2H) , 4.76 (m, 4H) , 4.19 (m, 2H) , 3.81 (s, 3H) , 3.81 (s, 3H) , 3.69 (s, 3H) , 2.69 (t, 1H) . LC/MS (m/z) : 294 (M+H)+.
  • 13
  • [ 5763-61-1 ]
  • [ 205444-22-0 ]
  • N-(3,4-dimethoxybenzyl)-4-iodo-6-(trifluoromethyl)pyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With triethylamine; In 1-methyl-pyrrolidin-2-one; at 100℃; for 0.333333h;Inert atmosphere; Microwave irradiation; To a solution of <strong>[205444-22-0]2-chloro-4-iodo-6-(trifluoromethyl)pyridine</strong> (1.0 g, 3.26 mmol) in NMP (5 mL) was added (3,4-dimethoxyphenyl)methanamine (2.45 mL, 16.29 mmol) and Et3N (2.26 mL, 16.29 mmol). The mixture was heated in a microwave at 100oC for 20 min. The reaction mixture was diluted with EA, washed with water and brine, dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (eluted with PE:EA = 15:1 to 10:1) to give the N-(3,4-dimethoxybenzyl) -4- iodo-6-(trifluoromethyl)pyridin-2-amine(400 mg, 28% yield) as a white solid. Retention time (LC-MS): 1.923 min. MH+ 439.
  • 14
  • [ 50-00-0 ]
  • [ 1198-14-7 ]
  • [ 5763-61-1 ]
  • 5-bromo-7-(((3,4-dimethoxybenzyl)amino)methyl)quinolin-8-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
21% The solution of 3,4-dimethoxybenzylamine (248 mu, 0.276 g, 1.65 mmol) in ethanol (4 mL) was added 37percent formaldehyde (62 mu, 0.049 g, 1.65 mmol). The mixture was stirred for 1 hour. Then the solution of <strong>[1198-14-7]5-bromoquinolin-8-ol</strong> (0.336 g, 1.5 mmol) in ethanol (5 mL) was added to the reaction mixture. After that the mixture was refluxed at 50°C for 72 hours. The reaction mixture was allowed to cool down and the obtained precipitate was filtered off, washed with ethanol and crystallized from ethanol to give the titled compound (0.130 g, 21 percent) as green crystals. Mp. 133-136 °C. 1 H NMR (300 MHz, CDCIs): delta 3.87 (d, 8H), 4.1 1 (s, 2H), 6.80-6.91 (m, 3H), 7.50-7.52 (m, 1 H), 7.65 (s, 1 H), 8.41 (d, 1 H), 8.82 (s, 1 H). 13C NMR (75 MHz, CDCI3): delta 52.0, 55.8, 55.9, 109.2, 1 10.9, 11 1.7, 119.5, 120.9, 121.0, 122.4, 127.1 , 129.6, 131.5, 135.4, 139.3, 148.4, 148.9, 152.0, 152.1. LCMS RT= 3.91 min. ESI+ m/z: 403.5 [M+H+].
  • 15
  • [ 5763-61-1 ]
  • [ 1521-41-1 ]
YieldReaction ConditionsOperation in experiment
92% With tert.-butylhydroperoxide; caesium carbonate; In water; acetonitrile; for 4h;Reflux; General procedure: To a solution of 4-methoxybenzyl amine (1.0 mmol) and cesium carbonate (1.0 mmol) in 3 mL of CH3CN was added a solution of 70% aqueous TBHP (3.0 mmol) and the mixture was refluxed for 4 h. The mixture was then dried to vacuum and extracted three times with ethyl acetate followed by washing with brine,and dried over anhydrous Na2SO4. Evaporation of the solvent under vacuum afforded the crude product, which was furthur purified by column chromatography using hexane/ethyl acetate mixture and then analyzed by spectroscopy.
  • 16
  • [ 889-31-6 ]
  • [ 5763-61-1 ]
  • [ 762-21-0 ]
  • 1-(3,4-dimethoxybenzyl)-4-hydroxy-5-oxo-2-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid ethyl ester [ No CAS ]
  • [ 873-95-0 ]
YieldReaction ConditionsOperation in experiment
63% With tert.-butylhydroperoxide; copper diacetate; In water; at 30℃; for 12h; General procedure: A mixture of N-benzyl enaminoketone (1.0 mmol), di-alkylacetylenedicarboxylate (1.0 mmol), benzyl amine (1.0 mmol), Cu(OAc)2 (8 mol%) and TBHP (4.0 mmol, 0.56 mL of a 70% aqueous solution) in water (0.5 mL) was stirred at 30 C for 12 h under air. The reaction progress was monitored by TLC. After completion of the reaction, the solid was filtrated out and washed with hot ethyl acetate. Finally the solvent of the filtrate was removed under vacuum and the resulting crude product was purified by column chromatography over 60-120 mesh silica gel [ethyl acetate/petroleum ether (60-80 C)].
  • 17
  • 3-(3,4-dimethoxybenzylamino)-5,5-dimethylcyclohex-2-enone [ No CAS ]
  • [ 5763-61-1 ]
  • [ 762-21-0 ]
  • 1-(3,4-dimethoxybenzyl)-2-(3,4-dimethoxy-phenyl)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylic acid ethyl ester [ No CAS ]
  • [ 873-95-0 ]
YieldReaction ConditionsOperation in experiment
68% With tert.-butylhydroperoxide; copper diacetate; In water; at 30℃; for 12h; General procedure: A mixture of N-benzyl enaminoketone (1.0 mmol), di-alkylacetylenedicarboxylate (1.0 mmol), benzyl amine (1.0 mmol), Cu(OAc)2 (8 mol%) and TBHP (4.0 mmol, 0.56 mL of a 70% aqueous solution) in water (0.5 mL) was stirred at 30 C for 12 h under air. The reaction progress was monitored by TLC. After completion of the reaction, the solid was filtrated out and washed with hot ethyl acetate. Finally the solvent of the filtrate was removed under vacuum and the resulting crude product was purified by column chromatography over 60-120 mesh silica gel [ethyl acetate/petroleum ether (60-80 C)].
 

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