[ CAS No. 3913-23-3 ] {[proInfo.proName]}

Name: 3913-23-3|2-(Bromomethyl)-1-methoxy-4-nitrobenzene|95%
Brand: Ambeed
SKU: A355798
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Quality Control of [ 3913-23-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 3913-23-3 ]

CAS No. :	3913-23-3	MDL No. :	MFCD00007329
Formula :	C₈H₈BrNO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JRHMPHMGOGMNDU-UHFFFAOYSA-N
M.W :	246.06	Pubchem ID :	77516
Synonyms :

Calculated chemistry of [ 3913-23-3 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.25
Num. rotatable bonds :	3
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	54.59
TPSA :	55.05 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.18 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.92
Log Po/w (XLOGP3) :	2.28
Log Po/w (WLOGP) :	2.35
Log Po/w (MLOGP) :	1.41
Log Po/w (SILICOS-IT) :	0.68
Consensus Log Po/w :	1.73

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.95
Solubility :	0.279 mg/ml ; 0.00113 mol/l
Class :	Soluble
Log S (Ali) :	-3.07
Solubility :	0.208 mg/ml ; 0.000845 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.17
Solubility :	0.167 mg/ml ; 0.000679 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	3.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.87

Safety of [ 3913-23-3 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	3261
Hazard Statements:	H314	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 3913-23-3 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 3913-23-3 ]
Downstream synthetic route of [ 3913-23-3 ]

[ 3913-23-3 ] Synthesis Path-Upstream 1~8

1
[ 50-00-0 ]
[ 100-17-4 ]
[ 3913-23-3 ]

Yield	Reaction Conditions	Operation in experiment
60%	at 28 - 85℃; for 20 h;	Example 8: Synthesis of Compound XIII-6; Step 1: Synthesis of 2-(bromomethyI)-l-methoxy-4-nitrobenzene (2); A mixture of p-nitro anisole (1, 1 g, 6.529 mmol), paraformaldehyde (0.218 g), sodium bromide (0.8 g) in glacial acetic acid (1.3 mL) was heated to 85 °C. H₂SO₄ (0.8 mL) and glacial acetic acid (0.8 mL) were gradually added to the mixture over 5 h. The resulting reaction mixture was then stirred for 3 h at 85 °C and then for 12 h at 28 °C. After completion of the reaction, the reaction mixture was extracted with diethyl ether and the ethereal extract was washed successively with 5percent NaHC0₃ solution and water, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to afford 2-(bromomethyl)- l-methoxy-4-nitrobenzene (2, 0.965 g, 60 percent). NMR (400 MHz, CDC1₃): δ 8.30-8.22 (m, 2H), 7.00- 6.95 (d, 1 H), 4.55 (s, 2H), 4.05 (s, 3H).

Reference： [1] Patent: WO2011/140338, 2011, A1, . Location in patent: Page/Page column 56-57
[2] Journal of Medicinal Chemistry, 1981, vol. 24, # 12, p. 1471 - 1475
[3] ACS Medicinal Chemistry Letters, 2014, vol. 5, # 5, p. 527 - 532

2
[ 5804-49-9 ]
[ 3913-23-3 ]

Reference： [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 18, p. 6254 - 6276
[2] Anales de la Real Sociedad Espanola de Fisica y Quimica, 1932, vol. 30, p. 767,775
[3] Patent: US5382590, 1995, A,

3
[ 25016-02-8 ]
[ 3913-23-3 ]

Reference： [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 18, p. 6254 - 6276

4
[ 39224-61-8 ]
[ 3913-23-3 ]

Reference： [1] Anales de la Real Sociedad Espanola de Fisica y Quimica, 1932, vol. 30, p. 767,775

5
[ 100-17-4 ]
[ 3913-23-3 ]

Reference： [1] Anales de la Real Sociedad Espanola de Fisica y Quimica, 1932, vol. 30, p. 767,775

6
[ 7383-11-1 ]
[ 3913-23-3 ]

Reference： [1] Anales de la Real Sociedad Espanola de Fisica y Quimica, 1932, vol. 30, p. 767,775

7
[ 5804-49-9 ]
[ 10035-10-6 ]
[ 3913-23-3 ]

Reference： [1] Anales de la Real Sociedad Espanola de Fisica y Quimica, 1932, vol. 30, p. 767,775

8
[ 3913-23-3 ]
[ 5804-49-9 ]

Reference： [1] Chemistry - A European Journal, 2001, vol. 7, # 5, p. 959 - 971

[ 3913-23-3 ] Synthesis Path-Downstream 1~88

1
[ 693-95-8 ]
[ 3913-23-3 ]
[ 77-78-1 ]
N-(2-methoxy-5-nitrobenzyl)-N-(1-methylthio-2-propenyl)formamide [ No CAS ]

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,1983,vol. 39,p. 805 - 808

2
[ 1779-81-3 ]
[ 3913-23-3 ]
[ 143543-78-6 ]

Reference： [1]Bioscience, Biotechnology and Biochemistry,1992,vol. 56,p. 1062 - 1065

3
[ 50-00-0 ]
[ 100-17-4 ]
[ 3913-23-3 ]

Yield	Reaction Conditions	Operation in experiment
60%	With sulfuric acid; acetic acid; sodium bromide; at 28 - 85℃; for 20h;	Example 8: Synthesis of Compound XIII-6; Step 1: Synthesis of 2-(bromomethyI)-l-methoxy-4-nitrobenzene (2); A mixture of p-nitro anisole (1, 1 g, 6.529 mmol), paraformaldehyde (0.218 g), sodium bromide (0.8 g) in glacial acetic acid (1.3 mL) was heated to 85 C. H2SO4 (0.8 mL) and glacial acetic acid (0.8 mL) were gradually added to the mixture over 5 h. The resulting reaction mixture was then stirred for 3 h at 85 C and then for 12 h at 28 C. After completion of the reaction, the reaction mixture was extracted with diethyl ether and the ethereal extract was washed successively with 5% NaHC03 solution and water, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to afford 2-(bromomethyl)- l-methoxy-4-nitrobenzene (2, 0.965 g, 60 %). NMR (400 MHz, CDC13): delta 8.30-8.22 (m, 2H), 7.00- 6.95 (d, 1 H), 4.55 (s, 2H), 4.05 (s, 3H).

Reference： [1]Patent: WO2011/140338,2011,A1 .Location in patent: Page/Page column 56-57
[2]Journal of Medicinal Chemistry,1981,vol. 24,p. 1471 - 1475
[3]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 527 - 532

4
[ 85006-25-3 ]
[ 3913-23-3 ]
C₁₈H₂₆N₂O₈ [ No CAS ]

Reference： [1]Tetrahedron Letters,1994,vol. 35,p. 6021 - 6024

5
[ 3913-23-3 ]
[ 50741-92-9 ]

Reference： [1]Journal of Organic Chemistry,1993,vol. 58,p. 6908 - 6910

6
[ 889675-13-2 ]
[ 3913-23-3 ]
[3-aminooxalyl-1-(2-methoxy-5-nitro-benzyl)-2-methyl-1H-indol-4-yloxy]-acetic acid tert-butyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 1737 - 1749

7
tert-butyl 4-({3-[amino(oxo)acetyl]-2-methyl-1H-indol-5-yl}oxy)butanoate [ No CAS ]
[ 3913-23-3 ]
4-[3-aminooxalyl-1-(2-methoxy-5-nitro-benzyl)-2-methyl-1H-indol-5-yloxy]-butyric acid tert-butyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 1737 - 1749

8
[ 3913-23-3 ]
[ 158144-85-5 ]
[ 954123-81-0 ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium hydride; In N,N-dimethyl-formamide; at 0 - 20℃; for 1.5h;	tert-Butyl 4-((2-methoxy-5-nitrobenzyloxy)methyl)-4-phenylpiperidine-1-carboxylate. 2-(Bromomethyl)-1-methoxy-4-nitrobenzene (100.0 mg, 0.34 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (93.0 mg, 0.38 mmol) were combined in dimethylformamide (4 mL) and cooled to 0 C. The reaction was treated with sodium hydride (9.0 mg, 0.38 mmol), stirred at 0 C. for 1 hr and at room temperature for 30 min. The reaction mixture was diluted with water and extracted with ethyl acetate (2×). The organic layers were pooled together, washed with brine (2×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (15% ethyl acetate/hexanes) gave 110 mg (71%). 1H-NMR (CDCl3, 500 MHz) delta 8.11 (dd, J=6.1, 3.1 Hz, 1H), 8.08 (d, J=2.8 Hz, 1H), 7.34 (m, 4H), 7.21-7.24 (m, 1H), 6.80 (d, J=8.9 Hz, 1H), 4.37 (s, 2H), 3.85 (s, 3H), 3.74-3.75 (m, 2H), 3.48 (s, 2H), 3.02-3.07 (m, 2H), 2.21-2.24 (m, 2H), 1.87-1.93 (m, 2H), 1.43 (s, 9H). Mass spec.: 479.16 (MNa)+.

Reference： [1]Patent: US2007/249607,2007,A1 .Location in patent: Page/Page column 73

9
[ 3913-23-3 ]
2-Methoxy-5-nitrobenzyl (4-{2-[(chlorocarbonyl)oxy]ethoxy}-5-methoxy-2-[(phenylacetyl)amino]methyl}phenyl)acetate [ No CAS ]

Reference： [1]Chemistry - A European Journal,2001,vol. 7,p. 959 - 971

10
[ 3913-23-3 ]
2-Methoxy-5-nitrobenzyl (5-methoxy-4-(2-[(4-nitrophenoxy)carbonyl]oxy}ethoxy)-2-[(phenylacetyl)amino]methyl}phenyl)acetate [ No CAS ]

Reference： [1]Chemistry - A European Journal,2001,vol. 7,p. 959 - 971

11
[ 3913-23-3 ]
N-(2-Methoxy-5-nitro-benzyl)-hydroxylamine; compound with trifluoro-acetic acid [ No CAS ]

Reference： [1]Tetrahedron Letters,1994,vol. 35,p. 6021 - 6024

12
[ 39224-61-8 ]
[ 3913-23-3 ]

Reference： [1]Anales de la Real Sociedad Espanola de Fisica y Quimica,1932,vol. 30,p. 767,775

13
[ 100-17-4 ]
[ 3913-23-3 ]

Reference： [1]Anales de la Real Sociedad Espanola de Fisica y Quimica,1932,vol. 30,p. 767,775

14
[ 7383-11-1 ]
[ 3913-23-3 ]

Reference： [1]Anales de la Real Sociedad Espanola de Fisica y Quimica,1932,vol. 30,p. 767,775

15
3-benzhydryl-4-piperidone hydrochloride [ No CAS ]
[ 3913-23-3 ]
3-(diphenylmethyl)-1-(2-methoxy-5-nitrobenzyl)piperidin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium hydrogencarbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 30h;	A mixture of 9.1 g (30 mmol) of 3-benzhydryl-4-piperidinone hydrochloride, 7.38 g (30.0 mmol) of <strong>[3913-23-3]2-methoxy-5-nitrobenzyl bromide</strong> and 5 g (60 mmol) of sodium hydrogen carbonate in 40 ml of dimethylformamide (DMF) was stirred for 30 hours at room temperature.. To the reaction mixture were added 250 ml of ethyl acetate, 400 ml of water and 50 ml of hexane, the mixture was shaken, and the organic layer was separated, and washed with water.. The organic layer was dried over MgSO4 (anhydrous) and concentrated under reduced pressure.. ethanol was added to the residue and the precipitated crystals were collected by filtration and dried to obtain 12.0 g of the title compound as crystals (yield:93%). mp 119-120C.1H-NMR (CDCl3) delta: 2.42-4.50 (m, 2H), 2.54-2.67 (m, 2H), 2.78-2.82 (m, 2H), 3.44-3.50 (m, 1H), 3.56 (s, 2H), 3.87 (s, 3H), 4.56 (d, 1H, J=11.2Hz), 6.87 (d, 1H, J=8.8Hz), 7.05-7.32 (m, 10H), 8. 16 (dd, 1H, J=3.2Hz, J=2.8Hz), 8.33 (d, 1H). Elemental analysis: C26H26N2O4Calculated: C, 72.54; H, 6.09; N, 6.51. Found: C, 72.37; H, 5.92; N, 6.41.
93%	With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 20℃; for 30h;	A mixture of 11 (9.1 g, 30 mmol), 2-methoxy-5-nitrobenzylbromide (7.4 g, 30 mmol), NaHCO3 (5.0 g, 60 mmol) and DMF (40 mL) was stirred at room temperature for 30 h. After diluting with EtOAc (250 mL), hexane (50 mL) and H2O (400 mL), the phases were separated. The organic phase was washed with H2O, dried and concentrated. The residue was treated with EtOH to give 13v as colorless crystals (12.0 g, 93%). Mp 119-120 C. 1H NMR (CDCl3) delta: 2.42-4.50 (m, 2H), 2.54-2.67 (m, 2H), 2.78-2.82 (m, 2H), 3.44-3.50 (m, 1H), 3.56 (s, 2H), 3.87 (s, 3H), 4.56 (d, J = 11.2 Hz, 1H), 6.87 (d, J = 8.8 Hz, 1H), 7.05-7.32 (m, 10H), 8.14-8.17 (m, 1H), 8.33 (d, J = 2.8 Hz, 1H). Anal. Calcd for C26H26N2O4: C, 72.54; H, 6.09; N, 6.51. Found: C, 72.37; H, 5.92; N, 6.41.

Reference： [1]Patent: EP1460062,2004,A1 .Location in patent: Page 74
[2]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 5175 - 5182

16
3-(4,4'-difluorobenzhydryl)-4-piperidone hydrochloride [ No CAS ]
[ 3913-23-3 ]
3-[Bis(4-fluorophenyl)methyl]-1-(2-methoxy-5-nitrobenzyl)-4-piperidinone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 3h;	To a solution of 3 g of 3-[bis(4-fluorophenyl)methyl]-4-piperidinone hydrochloride and 2.46 g of <strong>[3913-23-3]2-methoxy-5-nitrobenzyl bromide</strong> in 20 ml of dimethylformamide was added 4.2 mg of potassium carbonate with stirring at room temperature.. After stirring for 3 hours, 50 ml of ethyl acetate and 50 ml of brine were added thereto.. The ethyl acetate layer was separated and washed with water, and the solvent was distilled off under reduced pressure.. The residue was purified by subjecting it to silica gel column chromatography (11 g, ethyl acetate: hexane = 1: 1) to obtain the title compound as an oil.1H-NMR (CDCl3) delta: 2.35-2.90 (m, 6H), 3.57 (s, 2H), 3.88 (s, 3H), 4.55 (d, 1H, J=11 Hz), 6.80-7.28, 8.15-8.35 (m, 11H).

Reference： [1]Patent: EP1460062,2004,A1 .Location in patent: Page 59

17
[ 3913-23-3 ]
[ 143-33-9 ]
2-methoxy-5-nitrophenylacetonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 80℃; for 0.166667h;	To a solution of <strong>[3913-23-3]2-methoxy-5-nitrobenzyl bromide</strong> (984 mg) in dimethylsulfoxide (5 mL) was added sodium cyanide (216 mg) and the mixture was stirred at 80 degrees for 10 minutes. To the reaction mixture was added water and the mixture was extracted with ethyl acetate: The organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried over anhydrous sodium sulfate, and concentrated to give the title compound having the following physical data. The obtained title compound was used to next reaction without further purification. TLC: Rf 0.30 (ethyl acetate : hexane = 3 : 7).

Reference： [1]Patent: EP1486491,2004,A1 .Location in patent: Page 71

18
[ 3913-23-3 ]
[ 143-33-9 ]
[ 99459-52-6 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; water; at 70℃; for 1.5h;	2-BROMOMETHYL-L-METHOXY-4-NITRO-BENZENE (25 g) was dissolved in warm EtOH (45 mL) and stirred while slowly adding a solution of NACN (6.0 g in 12 mL H20) at 70 C. After the addition was complete, the reaction was stirred at 70 C for 90 min. The inorganic solid, which separated on cooling, was collected and washed well with CH3CN. The CH3CN filtrate was filtered again giving further inorganic solid, and again washed with CH3CN. The FINAL CH3CN filtrate was evaporated giving a red-brown solid. This solid was triturated with CH2C12 until the washings were colorless. Evaporation of the CH2C12 filtrate gave (2- methoxy-5-nitrophenyl) -acetonitrile as a red-brown solid, which was used without further purification.

Reference： [1]Patent: WO2004/85425,2004,A1 .Location in patent: Page 125-126

19
[ 3913-23-3 ]
[ 5188-07-8 ]
[ 288151-80-4 ]

Yield	Reaction Conditions	Operation in experiment
	In DMF (N,N-dimethyl-formamide); for 16h;	Sodium thiomethoxide (0.469 g) was added to a solution of <strong>[3913-23-3]2-methoxy-5-nitrobenzyl bromide</strong> (1.5 g) in dimethylformamide (25 ml). The mixture was stirred for 16 h, solvent removed at reduced pressure and the residue dissolved in ethyl acetate and washed with water and brine, dried (Na2SO4) and solvent removed at reduced pressure to give the title compound (1.2 g) as a yellow solid

Reference： [1]Patent: US6699879,2004,B1 .Location in patent: Page/Page column 23

20
[ 3913-23-3 ]
[ 14062-18-1 ]
C₁₉H₂₁NO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hexamethyldisilazane; In tetrahydrofuran; at -70 - 20℃; for 16h;	EXAMPLE 7; 5-(2-furyl)-4-[2-(2-methoxy-5-nitrophenyl)-1-(4-methoxyphenyl)ethyl-1,3-thiazol-2-amine; Step A; NaHMDS (30.0 mL, 30.0 mmol) was added to a -70C solution of ethyl 4-methoxyphenyl acetate (5.83 g, 30.0 mmol) and <strong>[3913-23-3]2-methoxy-5-nitrobenzyl bromide</strong> (7.38 g, 30.0 mmol) in 200 mL of THF. The reaction mixture was stirred to rt over a period of 16 h after which time the solvent was evaporated and the residue partitioned between 150 mL of EtOAc and 20 mL of saturated ammonium chloride. The aqueous phase was washed 2 x 25 mL of EtOAc and the combined organic extracts were washed with brine (20 mL) and dried over MgS04. The organic phase was dried, concentrated and chromatographed (0-50% EtOAc/hexane) to afford the monoalkylated target.

Reference： [1]Patent: WO2005/97767,2005,A1 .Location in patent: Page/Page column 39-41

21
[ 110-91-8 ]
[ 3913-23-3 ]
[ 503183-44-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	With triethylamine; In tetrahydrofuran; water;	A. A solution of <strong>[3913-23-3]2-bromomethyl-1-methoxy-4-nitrobenzene</strong> (1.23 g, 5 mmol), triethylamine (0.3 mL) and morpholine (1.0 mL, 11.5 mmol) in 45 mL of THF was heated at 60 C. for 30 minutes. The solvent was evaporated in vacuo. The residue was mixed with water (20 mL) and extracted with ether. Organic layers was separated, dried over MgSO4 and concentrated in vacuo to yield a yellow solid (1.222 g, 97%), which was used in the next step without further purification.

Reference： [1]Patent: US2003/60453,2003,A1

22
[ 3913-23-3 ]
[ 591-35-5 ]
3-[(3,5-Dichlorophenoxy)methyl]-4-methoxyphenylamine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With HCl conc.; potassium carbonate; hydrazine hydrate;nickel; In methanol; ethanol; acetone;	3-[(3,5-Dichlorophenoxy)methyl]-4-methoxyphenylamine hydrochloride. A mixture of <strong>[3913-23-3]2-bromomethyl-1-methoxy-4-nitrobenzene</strong> (2.46 g, 0.01 M), 3,5-dichlorophenol (1.79 g, 0.011 M), and potassium carbonate (2.07 g, 0.015 M) in acetone (150 mL) was intensively stirred for 5 min, then dicyclohexano-18-crown-6 (80 mg) was added, and the whole was brought to reflux under continued stirring. After 4 h, the mixture was cooled to r.t., and stirring was continued for overnight. The solvent was evaporated in vacuo. A yellowish-white solid was triturated with water (200 mL) and stirred for 30 min. Liquids were removed from the flask using reversed filtration, and the resulting solid was diluted with EtOH (75 mL). To this suspension was added wet Ni Raney (2.0 g), and the whole was heated up to 60 C. A solution of hydrazine monohydrate (100%, 2.0 mL) in EtOH (5 mL) was added dropwise within 30 min under continued stirring. As soon as the mixture cleared, the whole was brought to reflux and kept under stirring for 1 h. The solution was cooled to room temperature, decanted from catalyst, and concentrated in vacuo. Oily residue was dissolved in MeOH (30 mL) and treated with HCl conc. (12 mL). The formed suspension was kept in the freezer overnight and then filtered. Microcrystals, yield 1.55 g. Filtrate was concentrated in vacuo, and the formed precipitate filtered to give additional amount of product (0.410 g). Total yield of the title compound was 1.960 g (59%).

Reference： [1]Patent: US2002/165275,2002,A1

23
[ 1336-21-6 ]
[ 68832-13-3 ]
[ 3913-23-3 ]
[ 7087-68-5 ]
[ 346732-23-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	In water; N,N-dimethyl-formamide;	a [(2R)-1-(2-Methoxy-5-Nitrobenzyl)Pyrrolidinyl]Methanol Hydrochloride To <strong>[3913-23-3]2-methoxy-5-nitrobenzyl bromide</strong> (6.11 g, 24.8 mmol) dissolved in N,N-dimethylformamide (25 mL) was added Hunig's base (3.5 g, 27.2 mmol) followed by R-(-)-2-pyrrolidinemethanol (2.4 g, 24.8 mmol) and the reaction mixture was stirred at room temperature for 16 h. The N,N-dimethylformamide was removed, the residue treated with water (100 mL) followed by aqueous ammonium hydroxide until basic and extracted with ethyl acetate (3100 mL). The ethyl acetate extracts were combined, washed with water (3100 mL), dried over magnesium sulphate, filtered, and evaporated to give the free base of the title compound as a yellow oil (6.0 g). Treatment of an ethanol solution of the free base with ethanol/hydrogen chloride afforded the title compound (7.4 g, 95%) as a light yellow solid; MS: m/z 267 [M+H]+.

Reference： [1]Patent: US2002/137750,2002,A1

24
[ 3913-23-3 ]
[ 1074-82-4 ]
[ 180080-49-3 ]

Yield	Reaction Conditions	Operation in experiment
94%	With hydrogenchloride; In N-methyl-acetamide; water; ethyl acetate;	Example 117 Synthesis of N-(2-methoxy-5-nitrophenylmethyl)phthalimide Potassium phthalimide (836 mg) was added to a solution of <strong>[3913-23-3]2-methoxy-5-nitrobenzyl bromide</strong> (1.01 g) in dimethylformamide (41 ml) and stirred at room temperature for 10 minutes. Water and 2 N HCl were added to the reaction mixture and extraction was performed with ethyl acetate; then, the organic layer was washed successively with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution, dried with anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was washed successively with ethyl acetate and hexane to give 1.2 g of the titled compound (yield, 94%). 1H-NMR(DMSO-d6) delta: 3.97(3H,s), 4.80(2H,s), 7.26(1H, d, J=9.3 Hz), 7.82-7.93(4H,m), 7.99(1H, d, J=2.9 Hz), 8.40(1H, dd, J=9.3, 2.9 Hz)

Reference： [1]Patent: US6534546,2003,B1

25
[ 3913-23-3 ]
[ 99459-52-6 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; diethyl ether; water;	10 cm3 of a 3.5M potassium cyanide solution are added to a solution of 6.2 g of <strong>[3913-23-3]2-methoxy-5-nitrobenzyl bromide</strong> in 60 cm3 of methanol. The mixture is stirred under reflux for 4 hours and then concentrated to dryness under reduced pressure. The residue obtained is taken up in 100 cm3 of diethyl ether and 100 cm3 of water. The organic phase is dried over magnesium sulphate and then concentrated to dryness under reduced pressure (2.7 kPa) at 35 C. The crude product obtained is purified by chromatography on 40 g of silica (0.065-0.200 mm) contained in a column 3 cm in diameter (eluent: methylene chloride), collecting 20 cm3 fractions. Fractions 3 to 8 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 C. 4.2 g of 2-methoxy-5-nitrophenylacetonitrile melting at 100 C. are thus obtained. <strong>[3913-23-3]2-Methoxy-5-nitrobenzyl bromide</strong> may be prepared in the following way:

Reference： [1]Patent: US5382590,1995,A

26
[ 3913-23-3 ]
[ 10496-75-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	In ethanol; water;	EXAMPLE K Preparation of 2-methoxy-5-nitrobenzylnitrile. To a solution of sodium cyanide (6 g, 121.9 mmole) in water (5.3 ml) at 70 C. was added in small portions with stirring a hot solution of 2-methoxy-5-nitrobenzylbromide (25 g., 101.6 mmole) in ethanol (15 ml). The reaction mixture was then refluxed for 1.5 hours, cooled, and filtered. The filter cake was washed with acetonitrile and the filtrate was evaporated in vacuo to yield 2-methoxy-5-nitrobenzylnitrile (19.5 g., 100 percent) as a tan solid. The product was characterized by: 13 C NMR (CDCl3) 161.4, 141.0, 125.7, 124.6, 119.8, 116.5, 110.2, 56.3, 18.8.

Reference： [1]Patent: US5756065,1998,A

27
[ 3913-23-3 ]
[ 294-90-6 ]
N-(2-methoxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	In chloroform;	EXAMPLE E Preparation of N-(2-methoxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecane. To a stirred chloroform solution (20 ml) containing 2.9 g of 1,4,7,10-tetraazacyclododecane (16.8 mmole) was added a chloroform solution (20 ml) containing 2.1 g of <strong>[3913-23-3]2-methoxy-5-nitrobenzyl bromide</strong> (8.5 mmole) in one portion. After stirring at room temperature for three hours the reaction mixture was filtered and the filtrate concentrated (in vacuo) to give a residue which was chromatographed (silica, Solvent System 3). The monoalkylated product was isolated in 79 percent yield (MP=154-156 C.), and characterized by: 13 C NMR (CDCl3) 162.47, 140.63, 127.92, 125.49, 124.53, 109.91, 55.88, 53.25, 50.90, 47.18, 45.45, 45.29.

Reference： [1]Patent: US5756065,1998,A

28
[ 882977-79-9 ]
[ 3913-23-3 ]
5,6-dichloro-1-(2-methoxy-5-nitro-benzyl)-2-(2,2,2-trifluoro-ethyl)-1H-benzoimidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	To 5,6-dichloro-2-(2>2,2-trifluoro-ethyl)-1 H-benzimidazole (387 mg) in DMF (5 ml_) was added potassium carbonate powder (596 mg) and 3-methoxy- 5-nitro-benzyl bromide (1.06 g). The resulting mixture was stirred at room temperature overnight. The reaction mixture was quenched with water, extracted with EtOAc, and dried over Na2SO4. The crude product was purified by silica gel chromatography (10% - 40% EtOAc/hexanes) to yield the title compound as a peach-colored solid.1H NMR (300 MHz, CDCI3): delta 8.25 (dd, 1 H1 J = 9.1 , 2.7 Hz), 7.91 (s, 1 H)1 7.58 (d, 1 H, J = 2.5 Hz), 7.33 (s, 1 H), 7.03 (d, 1 H, J = 9.1 Hz), 5.37 (s, 2H)1 4.01 (S1 3H), 3.82 (ABq, 2H, JAB = 9.7 Hz, DeltavAB = 17 Hz).

Reference： [1]Patent: WO2006/39215,2006,A2 .Location in patent: Page/Page column 67-68

29
[ 3913-23-3 ]
[ 89694-48-4 ]
[ 915697-41-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; for 23h;Heating / reflux;	Example 12a) Preparation of 4-chloro-1-methoxy-2-(2-methoxy-benzyl)-nitrobenzene<strong>[3913-23-3]2-Methoxy-5-nitrobenzyl bromide</strong> (3.23 g, 13.11 mmol) and 5-chloro-2-methoxyphenyl boronic acid (2.43 g, 13.11 mmol) are dissolved in THF (180 mL) and treated with Pd(PPh3)4 (0.72 g, 0.625 mmol). The reaction mixture is stirred under an atmosphere of argon in the dark and a solution of Na2CO3 (3.5 g, 33 mmol) in water (10 mL) is added and the reaction is heated to reflux for 23 hours. The reaction mixture is cooled to room temperature and filtered. The filtrate is evaporated and the residue purified by flash chromatography over EPO <DP n="27"/>silica gel eluting with 25:75 EtOAc:isohexane to afford 4-chloro-1-methoxy-2-(2-methoxy- benzyl)-nitrobenzene; MH+ = 308.

Reference： [1]Patent: WO2006/125593,2006,A1 .Location in patent: Page/Page column 25-26

30
[ 3913-23-3 ]
[ 53440-32-7 ]
[ 325798-41-2 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; at 20℃; for 12h;	<strong>[3913-23-3]2-Methoxy-5-nitrobenzyl bromide</strong> (Fluka, 1.86 g, 7.559 mmol) is added to 2-(l,4,5,6-tetrahydropyrimidin-2-yl)benzenethiol (Ig, 5.201 mmol) in EPO <DP n="48"/>methanol (60 ml) at room temperature, maintained for 12 hours concentrated and ether (10 ml) added, the resulting light yellow needles are collected and washed with ether to give 1.28 g of pure product.

Reference： [1]Patent: WO2006/133098,2006,A2 .Location in patent: Page/Page column 46-47; 6/18

31
[ 3913-23-3 ]
[ 603-35-0 ]
[ 908863-87-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 7552 - 7560
[2]Canadian Journal of Chemistry,2008,vol. 86,p. 1010 - 1018
[3]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 527 - 532

32
[ 3913-23-3 ]
[ 169206-55-7 ]
[ 917916-93-9 ]

Yield	Reaction Conditions	Operation in experiment
81%		1. Synthesis of 3-(2-methoxy-5-nitrobenzyl)-2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester (A8) Sodium hydride (82 mg, 60% dispersion in mineral oil, weight percent) was suspended under a nitrogen atmosphere in DMF (5 mL). Compound A3 (0.5 g, 1.95 mmol) was added thereto and the reaction mixture was stirred for 10 min at RT. <strong>[3913-23-3]2-Methoxy-5-nitrobenzyl bromide</strong> (485 mg, 1.97 mmol) was added thereto. The reaction mixture was stirred for 18 h at RT, combined with water and extracted with EtOAc. The combined organic phases were washed with sat. aq. NaCl solution, dried over Na2SO4 and the solvent was removed under a vacuum. The residue was dissolved in a mixture of ether and heptane. After removal of the ether, the desired product 3-(2-methoxy-5-nitrobenzyl)-2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester (A87) (670 mg, 81% of theoretical) was obtained as a white solid by filtration.

Reference： [1]Patent: US2009/105290,2009,A1 .Location in patent: Page/Page column 35

33
[ 15568-85-1 ]
[ 3913-23-3 ]
[ 666735-00-8 ]

Yield	Reaction Conditions	Operation in experiment
23%		2-Bromomethyl-1-methoxy-4-nitrobenzene (2.03 g) was dissolved in N,N-dimethylformamide (30 ml). Triethylamine (5 ml) and 20% palladium hydroxide (1.08 g) were added to the solution, and the mixture was stirred under a hydrogen gas atmosphere at room temperature overnight. The reaction mixture was filtered and was then washed with chloroform. The solvent was removed by distillation under the reduced pressure, water was added to the residue, and the organic layer was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue as such was used in the next reaction without purification. The residue and 5-methoxymethylene-2,2-dimethyl-[1,3]dioxan-4,6-dione (2.00 g) were suspended in 2-propanol (40 ml), and the suspension was stirred at 70C for 30 min. The reaction mixture was cooled to room temperature, and the precipitated crystal was then collected by filtration and was washed with methanol and then with ether. The crystal thus obtained as such was used in the next reaction without further purification. The crystal prepared above and biphenyl (5.9 g) were suspended in diphenyl ether (15 ml), and the suspension was stirred at 220C for 3 hr. The reaction mixture was cooled to room temperature, and the cooled reaction mixture as such was purified by column chromatography with an ethyl acetate-hexane system to give 6-methoxy-7-methyl-1H-quinolin-4-one (352 mg, yield 23%) (3 steps).

Reference： [1]Patent: EP1724268,2006,A1 .Location in patent: Page/Page column 63

34
3-benzhydryl-4-piperidone hydrochloride [ No CAS ]
[ 3913-23-3 ]
1-(5-amino-2-methoxybenzyl)-3-(diphenylmethyl)piperidin-4-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 5175 - 5182

35
[ 3913-23-3 ]
[ 1330634-08-6 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6254 - 6276

36
[ 3913-23-3 ]
[ 1330634-11-1 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6254 - 6276

37
[ 3913-23-3 ]
[ 243142-39-4 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6254 - 6276

38
[ 3913-23-3 ]
[ 1330633-65-2 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6254 - 6276

39
[ 3913-23-3 ]
[ 1330633-70-9 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6254 - 6276

40
[ 3913-23-3 ]
[ 68-11-1 ]
[ 243142-36-1 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6254 - 6276

41
[ 25016-02-8 ]
[ 3913-23-3 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6254 - 6276

42
[ 3913-23-3 ]
[ 1152844-08-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium azide; In N,N-dimethyl-formamide; at 20℃; for 12h;	Step 2: Synthesis of 2-(azidomethyl)-l-methoxy-4-nitrobenzene (3); 2-(bromomethyl)-l -methoxy-4-nitrobenzene (2, 0.2 g, 0.8128 mmol) was taken up in DMF (2 mL) to form a mixture, sodium azide (52 mg, 0.8128 mmol) was added to the mixture, and the mixture was stirred at room temperature for 12 h. The progress of the reaction was monitored by TLC and liquid chromtography-mass spectrometry (LCMS). After completion of the reaction, water was added and the product was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford 2-(azidomethyl)-l - methoxy-4-nitrobenzene (3, 0.161 g, 80 %), which was used in the next step without further purification. NMR (400 MHz, CDCI3): delta 8.30-8.20 (m, 2H), 7.00-6.95 (d, 1 H), 4.44 (s, 2H), 4.02 (s, 3H).

Reference： [1]Patent: WO2011/140338,2011,A1 .Location in patent: Page/Page column 56-57

43
[ 3913-23-3 ]
[ 40896-72-8 ]

Reference： [1]Patent: WO2011/140338,2011,A1

44
[ 3913-23-3 ]
[ 1346447-85-5 ]

Reference： [1]Patent: WO2011/140338,2011,A1

45
[ 3913-23-3 ]
[ 1346447-86-6 ]

Reference： [1]Patent: WO2011/140338,2011,A1

46
[ 3913-23-3 ]
[ 1346447-87-7 ]

Reference： [1]Patent: WO2011/140338,2011,A1

47
[ 3913-23-3 ]
guttiferone A [ No CAS ]
14-O-2-methoxy-5-nitrobenzylguttiferone A [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With potassium carbonate; In acetone; at 20℃;Inert atmosphere;	To a magnetically stirred solution of guttiferone A (30 mg, 0.050 mmol) in dry acetone were added under nitrogen atmosphere <strong>[3913-23-3]2-(bromomethyl)-1-methoxy-4-nitrobenzene</strong> (12 mg,0.05 mmol) and potassium carbonate (68 mg, 0.50 mmol). The reaction mixture was allowed to room temperature overnight. The reaction mixture was quenched using water, then extracted with dichloromethane. The organic layer was washed with water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The crude was passed through a silica column (MeOH/DCM gradient) to afford 14-O-2-methoxy-5-nitrobenzyl-guttiferone A (20.49 mg, 53% yield) as a yellow oil.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 65,p. 284 - 294

48
[ 3913-23-3 ]
guttiferone A [ No CAS ]
13,14-bis-O-2-methoxy-5-nitrobenzylguttiferone A [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With potassium carbonate; caesium carbonate; In acetone; at 0 - 20℃;Inert atmosphere;	To a magnetically stirred solution of guttiferone A (20 mg, 0.033 mmol) in dry acetone were added at 0 C under nitrogen atmosphere <strong>[3913-23-3]2-(bromomethyl)-1-methoxy-4-nitrobenzene</strong> (81 mg,0.33 mmol), potassium carbonate (45 mg, 0.33 mmol) and cesium carbonate (10 mg, 0.033 mmol). The reaction mixture was allowed to room temperature overnight. The reaction mixture was quenched using water, then extracted with dichloromethane. The organic layer was washed with water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The crude was passed through a silica column (MeOH/DCM gradient) to afford 13,14-bis-O-2-methoxy-5-nitrobenzyl-guttiferone A (11.76 mg, 39% yield) as a yellow oil.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 65,p. 284 - 294

49
(6-bromo-1H-indol-3-yl)acetic acid ethyl ester [ No CAS ]
[ 3913-23-3 ]
[ 1542274-19-0 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 2074 - 2090

50
[ 3913-23-3 ]
[ 1542274-23-6 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 2074 - 2090

51
[ 3913-23-3 ]
[ 1542274-21-4 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 2074 - 2090

52
[ 3913-23-3 ]
[ 96-41-3 ]
[ 1569737-21-8 ]