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Chemical Structure| 3970-39-6 Chemical Structure| 3970-39-6

Structure of 3970-39-6

Chemical Structure| 3970-39-6

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Product Details of [ 3970-39-6 ]

CAS No. :3970-39-6
Formula : C7H6ClNO3
M.W : 187.58
SMILES Code : ClC1=C(C=CC=C1[N+](=O)[O-])OC
MDL No. :MFCD11035883
Boiling Point : No data available
InChI Key :XVBAPYDWAVGVGW-UHFFFAOYSA-N
Pubchem ID :12411827

Safety of [ 3970-39-6 ]

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

Computational Chemistry of [ 3970-39-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 46.77
TPSA ?

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

55.05 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.55
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

1.49
Log Po/w (WLOGP)?

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

2.26
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.

1.21
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

0.32
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.37

Water Solubility

Log S (ESOL):?

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

-2.18
Solubility 1.24 mg/ml ; 0.00661 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.

-2.25
Solubility 1.05 mg/ml ; 0.00558 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

-2.52
Solubility 0.561 mg/ml ; 0.00299 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.

-6.39 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

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)

2.03

Application In Synthesis of [ 3970-39-6 ]

* 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 [ 3970-39-6 ]

[ 3970-39-6 ] Synthesis Path-Downstream   1~36

  • 2
  • [ 577-19-5 ]
  • [ 3970-39-6 ]
  • [ 106166-92-1 ]
  • 3
  • [ 610-97-9 ]
  • [ 3970-39-6 ]
  • [ 855255-34-4 ]
  • 5
  • [ 3970-39-6 ]
  • [ 113206-03-4 ]
YieldReaction ConditionsOperation in experiment
100% With iron; acetic acid; In ethanol; for 3.5h;Heating / reflux; 2-Chloro-3-nitroanisole C3 (1.38 g; 7.36 MMOL) was dissolved in a mixture of glacial acetic acid (19 ML)/ETHANOI (19 mL). To this solution was added iron powder (1.64 g; 29.4 MMOL). The mixture was stirred at reflux for 3.5 hr and worked up. The reaction mixture was diluted with water (70 mL), neutralized with solid NA2CO3 and the product extracted with CH2CI2 (3X 150 mL). The extracts were combined and washed with saturated. brine and then dried(NA2SO4), filtered and concentrated in vacuo to afford the crude product, 2-chloro-3-methoxyaniline C4 (100%; 1.2 g) as a yellow oil. This material was used as such in the following steps. MS 157.9 (MH) + ; Homogeneity by HPLC (TFA) 220 nm: 86%.
100% With iron; acetic acid; In ethanol; for 3.5h;Heating / reflux; Step C:; 2-Chloro-3-nitroanisole 1c2 (1.38 g; 7.36 mmol) was dissolved in a mixture ofglacial acetic acid (19 mL)/ethanol (19 mL). To this solution was added iron powder(1.64 g; 29.4 mmol). The mixture was stirred at reflux for 3.5 hr and worked up. Thereaction mixture was diluted with water (70 ml_), neutralized with solid Na2CO3 and theproduct extracted with CH2CI2 (3 X 150 ml). The extracts were combined and washedwith sat. brine and then dried(Na2SO4), filtered and concentrated in vacua toafford the crude product, 2-chloro-3-methoxyaniline 1c3 (100%; 1.2 g) as a yellow oil.This material was used as such in the following steps. MS 157.9 (MH)+; Homogeneityby HPLC (TFA) (at) 220nm: 86%.
100% With iron; acetic acid; In ethanol; for 3.5h;Heating / reflux; 2-Chloro-3-nitroanisole 1c2 (1.38 g; 7.36 mmol) was dissolved in a mixture of glacial acetic acid (19 mL)/ethanol (19 mL). To this solution was added iron powder (1.64 g; 29.4 mmol). The mixture was stirred at reflux for 3.5 hr and worked up. The reaction mixture was diluted with water (70 mL), neutralized with solid Na2CO3 and the product extracted with CH2Cl2 (3*150 mL). The extracts were combined and washed with sat. brine and then dried(Na2SO4), filtered and concentrated in vacuo to afford the crude product, 2-chloro-3-methoxyaniline 1c3 (100%; 1.2 g) as a yellow oil. This material was used as such in the following steps. MS 157.9 (MH)+; Homogeneity by HPLC (TFA)a220 nm: 86%.
100% With iron; acetic acid; In ethanol; for 3.5h;Heating / reflux; 2-Chloro-3-nitroanisole 2c2 (1.38 g; 7.36 mmol) was dissolved in a mixtureof glacial acetic acid (19 ml_ )/ethanol (19 ml_). To this solution was added ironpowder (1.64 g; 29.4 mmol). The mixture was stirred at reflux for 3.5 hr and workedup. The reaction mixture was diluted with water (70 ml), neutralized with solidNa2CO3 and the product extracted with CH2CI2( 3X 150 ml). The extracts werecombined and washed with sat. brine and then dried(Na2SO4), filtered andconcentrated in vacua to afford the crude product, 2-chloro-3-methoxyaniline 2c3(100%; 1.2 g) as a yellow oil. This material was used as such in the following steps.MS 157.9 (MH)+; Homogeneity by HPLC (TFA) (at) 220nm: 86%.
With iron; acetic acid; at 45 - 80℃; for 2h; (iii) Iron powder (3.63 g, 65.0 mmol) was suspended in acetic acid (50 ml) and warmed to 4O0C with mechanical stirring. 2-Chloro-3-nitrophenyl methyl ether (2.44 g, 13.01 mmol) dissolved in acetic acid (25 ml) was added at such a rate as to maintain a temperature of 45-5O0C. The mixture was heated at 80 0C for 2 hours after the addition had been completed. The mixture was filtered through celite and concentrated in vacuo. The residue was partitioned between ethyl acetate and 10% 0.880 ammonia solution. Solids were removed by filtration through celite and the aqueous extracted in to ethyl acetate (x3). The combined extracts were washed with water, brine, dried over anhydrous sodium sulfate and concentrated to an oil. The crude product was purified by flash-silica gel chromatography, eluting with a 0-100% gradient of ethyl acetate in isohexane to afford 2-chloro-3-(methyloxy)aniline (1.66 g).

  • 6
  • [ 16554-45-3 ]
  • [ 3970-39-6 ]
YieldReaction ConditionsOperation in experiment
b) 2-Chloro-1-methoxy-3-nitro-benzene; To a mixture consisting of 15.5g (92. 26mmol) 2-methoxy-6-nitro-phenylamine, 31 ml water and 31ml conc. HCI, a solution of 6.36g (92. 26mmol) NaNO2 in 38ml water is slowly added dropwise at-10C-0C. After stirring for 0.5h the mixture is slowly added to a solution of 11.88g (120mol) CuCI in 93ml conc. HCI. After completion of the addition stirring is continued for 1.5h at room temperature and for 0.5h at reflux temperature. The reaction mixture is allowed to cool to room temperature and is poured on water and extracted (3x) with ethyl acetate. The combined organic layers are washed with water (2x) and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue is purified by flash- chromatography on silica gel (hexane: EtOAc = 3: 1) to afford 12. 6g of the title compound as a crystalline solid.
16.5 g INTERMEDIATE: (5-Methoxy-3-methyl-quinoxalin-2-yl)-hydrazine (lie). 2-Methoxy-6-nitro- phenylamine (25.0 g) was dissolved in 37% aq HC1, and the mixture ws cooled on an ice/water bath. A solution of NaN02 (11.8 g) in water (3 mL) was added, and the resulting mixture was stirred at 0 C for 15 min. The reaction mixture was added to a solution of cuprous monochloride (14.7 g) in 37% aq HC1 (10 mL) under stirring at 45-50 C. The resulting mixture was stirred at 50 C for 15 min, cooled at 5 C for 15 min. The solid was filtered off and dried to give 2-chloro-l-methoxy-3- nitrobenzene (16.5 g). A mixture of 16 g of this material, racemic alanine (17 g), and K2CO3 (12 g) was heated in DMSO (180 mL) at 100 C for 24h. The volatiles were removed using a freeze dryer. The residue was acidified with 2M aq HC1 (50 mL) and extracted into EtOAc. The organic extract was extracted with 2M aq Na2C03 and water. The combined aq extracts were acidified with 2M aq HC1 and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO i, filtered, and concentrated in vacuo to afford 2-(2-methoxy-6-nitro-phenylamino)-propionic acid. This material was dissolved in ethanol (600 mL) and 96%> sulphuric acid (6 mL) was added. The mixture was heated at 80 C overnight. The volatiles were removed in vacuo and the residue was dissolved in EtOAc and washed with 2M aq Na2C03. The organic layer was dried over MgSO i, filtered, and concentrated in vacuo to afford 2-(2-methoxy-6-nitro-phenylamino)-propionic acid ethyl ester (8.0 g). This material was dissolved in ethanol (300 mL) and 5% palladium on carbon was added. The mixture was treated with 3 bars of hydrogen pressure on a Parr shaker for 3h. The catalyst was filtered off, and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica (eluent: heptanes? EtOAc) to afford 5-methoxy-3-methyl-3,4-dihydro- lH-quinoxalin-2-one (3.0 g). This material was dissolved in ethanol (300 mL) and treated with 30% aq hydrogen peroxide at 80 C overnight. Most of the volatiles were removed in vacuo. The residue was suspended in ethanol (10 mL) and cooled on an ice/water bath before the solid was filtered off, washed with ice-cold ethanol, and dried to afford 5-methoxy-3-methyl-lH-quinoxalin-2-one (2.2 g). This material was dissolved in phosphoryl chloride (24 mL) and heated at 130 C for 2h. The volatiles were removed in vacuo. The residue was partitioned between chloroform and ice + 2M aq NaOH. The organic layer was dried over MgSO i, filtered, and concentrated in vacuo to afford 2- chloro-5-methoxy-3-methyl-quinoxaline (2.5 g). This material was dissolved in ethanol (22 mL), hydrazine hydrate (2.9 mL) was added, and the mixture was refluxed for 2h. The volatiles were removed in vacuo, and water was added. The solid was filtered off, washed with water and heptanes and dried to afford lie (1.70 g) sufficiently pure for the next step.
  • 7
  • [ 3970-39-6 ]
  • [ 98-95-3 ]
  • [ 137465-71-5 ]
  • 8
  • [ 603-84-9 ]
  • [ 77-78-1 ]
  • [ 3970-39-6 ]
  • 9
  • [ 603-84-9 ]
  • [ 74-88-4 ]
  • [ 3970-39-6 ]
YieldReaction ConditionsOperation in experiment
98% With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 18 - 22℃; The nitrophenol starting material C2 (1.3 g; 7.49 MMOL) was dissolved in DMF (10 mL) and to this solution was added ground cesium carbonate (2.92 g; 8.96 MMOL), followed by Mel (1. 4 mL; 22. 5 MMOL). The mixture was stirred at room temperature overnight. The DMF was evaporated in vacuo and the residue taken up in ether (150 ML), washed with water (150 mL), brine (4x 100 mL), and then dried(MGSO4) THE organic phase was filtered and evaporated to afford the crude 2- CHLORO-3-NITROANISOLE C3 (98%; 1.38 g) as an orange solid. Homogeneity by HPLC (TFA) 220 nm: 93%.
98% With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; Step B:; The nitrophenol starting material 1c1 (1.3 g; 7.49 mmol) was dissolved inDMF (10 ml) and to this solution was added ground cesium carbonate (2.92 g; 8.96mmol), followed by Mel (1.4 ml; 22.5 mmol). The mixture was stirred at roomtemperature overnight. The DMF was evaporated in vacuo and the residue taken upin ether (150 ml), washed with water (150 ml), brine (4 X 100 mL), and then driedover (MgSO4). The organic phase was filtered and evaporated to afford the crude 2-chloro-3-nitroanisole 1c2 (98%; 1.38 g) as an orange solid.
98% With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; The nitrophenol starting material 1c1 (1.3 g; 7.49 mmol) was dissolved in DMF (10 mL) and to this solution was added ground cesium carbonate (2.92 g; 8.96 mmol), followed by MeI (1.4 mL; 22.5 mmol). The mixture was stirred at room temperature overnight. The DMF was evaporated in vacuo and the residue taken up in ether (150 mL), washed with water (150 mL), brine (4×100 mL), and then dried(MgSO4). The organic phase was filtered and evaporated to afford the crude 2-chloro-3-nitroanisole 1c2 (98%; 1.38 g) as an orange solid.
98% With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; The nitrophenol starting material 2c1 (1.3 g; 7.49 mmol) was dissolved inDMF (10 ml) and to this solution was added ground cesium carbonate (2.92 g; 8.96mmol), followed by Mel (1.4 ml; 22.5 mmol). The mixture was stirred at roomtemperature overnight. The DMF was evaporated in vacua and the residue taken upin ether (150 ml), washed with water (150 ml), brine (4 X 100 ml), and then driedover (MgSO4). The organic phase was filtered and evaporated to afford the crude 2-chloro-3-nitroanisole 2c2 (98%; 1.38 g) as an orange solid.Homogeneity by HPLC (TFA) (at) 220nm: 93%.
With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; 3-Nitrophenol (10 g, 72 mmol) was dissolved in hot concentrated hydrochloric acid (100 ml) and cooled rapidly (ice-brine bath) to give a fine suspension. Potassium chlorate (8.8 g, 72 mmol) was dissolved in water (100 ml) and added to the mixture and stirring continued at 0C for 2 hours. The reaction mixture was extracted with ethyl acetate (2X100 ml) and the combined organic extracts washed with water (100 ml), brine (100 ml), dried over sodium sulfate and evaporated in vacuo (water bath temp <45C) to give 2-chloro-3-nitrophenol (not purified) (Rf 0. 38,33% EtOAc/Pet spirit). The crude residue was dissolved in DMF and to this was added potassium carbonate (19.3 g, 140 mmol) and methyl iodide (5.6 ml, 90 mmol). The reaction mixture was stirred overnight at room temperature before diluting with ethyl acetate (200 ml) and washing with water (4X100 ml) and brine (100 ml). The organic phase was dried over sodium sulfate to give 2-chloro-3-nitroanisole (not purified) (Rf 0. 61. 33% EtOAc/Pet spirit). The crude residue obtained was dissolved in 2-aminoethylmorpholine 15.7 ml, 120 mmol) and butanol (50 ml) and heated at 100C for 16 hours under an atmosphere of nitrogen. Excess reagent and solvent were removed in vacuo and the residue diluted with EtOAc (200 ml) and 1M NaOH (100 ml). The organic phase was separated and the remaining aqueous solution extracted with EtOAc (2X100 ml). The organic extracts were combined and washed with brine (100 ml), dried over sodium sulfate, filtered and evaporated. The crude product was columned (silica) using a gradient from petroleum spirit to EtOAc (Rf 0.17, 50% EtOAc/Pet Spirit) to give 2-methoxy-N-(2-morpholinoethyl)-6- nitrobenzenamine (7.0 g, 35% yield over 3 steps). ESMS 282 (M+H).
With potassium carbonate; In acetone; at 70℃; for 4h; (ii) 2-Chloro-3-nitrophenol (2.61 g, 15.04 mmol) and potassium carbonate (3.12 g, 22.56 mmol) were suspended in acetone (50 ml). Methyl iodide (1.034 ml, 16.54 mmol) was added and the mixture heated at 70 0C for 4 hours. The solids were filtered, washed with acetone and the filtrate concentrated to a solid. The crude product was purified by flash-silica gel chromatography, eluting with a 0-100% gradient of ethyl acetate in isohexane to afford 2-chloro-3-nitrophenyl methyl ether (2.44 g).

  • 10
  • [ 75-15-0 ]
  • [ 3970-39-6 ]
  • [ 908355-82-8 ]
  • 11
  • [ 74-93-1 ]
  • [ 3970-39-6 ]
  • [ 65516-73-6 ]
  • 16
  • [ 562-54-9 ]
  • potassium-<2-chloro-3-nitro-phenolate> [ No CAS ]
  • [ 3970-39-6 ]
  • 17
  • [ 3970-39-6 ]
  • [ 98-95-3 ]
  • copper-powder [ No CAS ]
  • [ 137465-71-5 ]
  • 19
  • [ 3970-39-6 ]
  • acetic acid-(2-chloro-3-nitro-phenyl ester) [ No CAS ]
  • 20
  • [ 3970-39-6 ]
  • benzoic acid-(2-chloro-3-nitro-phenyl ester) [ No CAS ]
  • 23
  • [ 3970-39-6 ]
  • [ 20275-29-0 ]
  • 24
  • [ 3970-39-6 ]
  • [ 105972-27-8 ]
  • 25
  • [ 3970-39-6 ]
  • [ 109185-49-1 ]
  • 28
  • [ 3970-39-6 ]
  • [ 2942-19-0 ]
  • 29
  • [ 3970-39-6 ]
  • [ 65516-92-9 ]
  • 30
  • (2-aminoethyl)morpholine [ No CAS ]
  • [ 3970-39-6 ]
  • 2-methoxy-N-(2-morpholinoethyl)-6-nitrobenzenamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
35% In butan-1-ol; at 100℃; for 16h; 3-Nitrophenol (10 g, 72 mmol) was dissolved in hot concentrated hydrochloric acid (100 ml) and cooled rapidly (ice-brine bath) to give a fine suspension. Potassium chlorate (8.8 g, 72 mmol) was dissolved in water (100 ml) and added to the mixture and stirring continued at 0C for 2 hours. The reaction mixture was extracted with ethyl acetate (2X100 ml) and the combined organic extracts washed with water (100 ml), brine (100 ml), dried over sodium sulfate and evaporated in vacuo (water bath temp <45C) to give 2-chloro-3-nitrophenol (not purified) (Rf 0. 38,33% EtOAc/Pet spirit). The crude residue was dissolved in DMF and to this was added potassium carbonate (19.3 g, 140 mmol) and methyl iodide (5.6 ml, 90 mmol). The reaction mixture was stirred overnight at room temperature before diluting with ethyl acetate (200 ml) and washing with water (4X100 ml) and brine (100 ml). The organic phase was dried over sodium sulfate to give <strong>[3970-39-6]2-chloro-3-nitroanisole</strong> (not purified) (Rf 0. 61. 33% EtOAc/Pet spirit). The crude residue obtained was dissolved in 2-aminoethylmorpholine 15.7 ml, 120 mmol) and butanol (50 ml) and heated at 100C for 16 hours under an atmosphere of nitrogen. Excess reagent and solvent were removed in vacuo and the residue diluted with EtOAc (200 ml) and 1M NaOH (100 ml). The organic phase was separated and the remaining aqueous solution extracted with EtOAc (2X100 ml). The organic extracts were combined and washed with brine (100 ml), dried over sodium sulfate, filtered and evaporated. The crude product was columned (silica) using a gradient from petroleum spirit to EtOAc (Rf 0.17, 50% EtOAc/Pet Spirit) to give 2-methoxy-N-(2-morpholinoethyl)-6- nitrobenzenamine (7.0 g, 35% yield over 3 steps). ESMS 282 (M+H).
  • 31
  • [ 3970-39-6 ]
  • [ 109-85-3 ]
  • [ 860466-30-4 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; at 180℃; for 0.416667h; c) (2-Methoxy-ethyl)- (2-methoxy-6-nitro-phenyl)-amine; A mixture of 7.5g (40mol) <strong>[3970-39-6]2-chloro-1-methoxy-3-nitro-benzene</strong>, 14ml diisopropylethylamine and 35ml 2-methoxyethyl amine is heated (180C oil bath temperature) in a closed steel reactor for 25 min. Then the reaction mixture is cooled to room temperature and is concentrated in vacuo (3 x coevaporation with toluene) to obtain ca. 20g (which contains 85% of the title compound) of a red oil which is used without further purification in the next step.
  • 32
  • [ 3970-39-6 ]
  • [ 146012-36-4 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; zinc; In tetrahydrofuran; a. 2,2'-Dichloro-3,3'-dimethoxyhydrazobenzene To a stirred solution of THF (30 ml) and <strong>[3970-39-6]2-chloro-3-methoxynitrobenzene</strong> (10 g, 53.3 mM), was added 50% NaOH (2.5 ml, 62.5 mM) and the resultant solution was heated to 65 C. Zinc dust (8.0 g, 0.12 mM) was added by portions, ensuring that reaction temperature remained below 70 C. Following the addition, the reaction was maintained at 65 C. for 30 minutes. To this mixture was added 10% NaOH (40 ml, 0.1M) and additional zinc dust (10.5 g, 0.16M). The resulting mixture was stirred at 65 C. for 3 hours and then cooled to room temperature. Ether (100 ml) was then added, the mixture stirred, and the ether decanted. This procedure was repeated twice. The ether fractions were combined and dried over MgSO4, filtered, and the solvent was concentrated under reduced pressure. This afforded the titled compound as a solid in quantitative yield and was used in the next step without further purification. MS(CI): 313 (m+1).
  • 33
  • [ 603-85-0 ]
  • [ 3970-39-6 ]
  • 34
  • [ 3970-39-6 ]
  • [ 30748-92-6 ]
  • 35
  • [ 3970-39-6 ]
  • [ 1427029-02-4 ]
  • 36
  • [ 3970-39-6 ]
  • [ 30748-89-1 ]
 

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