[ CAS No. 52414-98-9 ] {[proInfo.proName]}

Name: 52414-98-9|4-Bromo-2-methyl-1-nitrobenzene|97%
Brand: Ambeed
SKU: A221088
Price: 5.0 USD
Availability: InStock
Rating: 98 (30 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 52414-98-9

Structure of 52414-98-9 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 52414-98-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 52414-98-9 ]

SDS Specification

Alternatived Products of [ 52414-98-9 ]

Product Details of [ 52414-98-9 ]

CAS No. :	52414-98-9	MDL No. :	MFCD00137824
Formula :	C₇H₆BrNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PAHAIHXVVJMZKU-UHFFFAOYSA-N
M.W :	216.03	Pubchem ID :	81577
Synonyms :

Calculated chemistry of [ 52414-98-9 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	47.93
TPSA :	45.82 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.11 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.82
Log Po/w (XLOGP3) :	3.53
Log Po/w (WLOGP) :	2.67
Log Po/w (MLOGP) :	2.77
Log Po/w (SILICOS-IT) :	0.8
Consensus Log Po/w :	2.32

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.74
Solubility :	0.0392 mg/ml ; 0.000182 mol/l
Class :	Soluble
Log S (Ali) :	-4.18
Solubility :	0.0144 mg/ml ; 0.0000666 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-3.02
Solubility :	0.204 mg/ml ; 0.000946 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	1.8

Safety of [ 52414-98-9 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 52414-98-9 ]

* 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 [ 52414-98-9 ]
Downstream synthetic route of [ 52414-98-9 ]

[ 52414-98-9 ] Synthesis Path-Upstream 1~15

1
[ 52414-98-9 ]
[ 1196-69-6 ]

Reference： [1] Journal of Organic Chemistry, 1986, vol. 51, # 26, p. 5106 - 5110

2
[ 611-05-2 ]
[ 52414-98-9 ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: With hydrogen bromide; sodium nitrite In water; acetone at 0 - 5℃; for 0.166667 h; Stage #2: With copper(I) bromide In water; acetone at 15℃; for 0.25 h;	Preparation of 4-bromo~2-methyI-1-nitro-benzene (102):[0190] To an ice cold solution of 10.0 g (65.7 mmol) 3-methyl-4-nitro-phenylamine in 200 niL acetone, was added 21 niL (197.2 mmol) 48percent HBr. 4.54g (65.7 mmol) NaNO₂ was dissolved in 20 mL water and was added dropwise to the amine solution at a rate to keep the temperature under 5 °C. The mixture was stirred at this temperature for an additional 10 minutes then 1.5 g (10 mmol) solid CuBr was added portion-wise at a rate to keep the temperature under 15 °C. The reaction was complete when no EPO <DP n="94"/>more nitrogen evaluated (about 15 minutes). The reaction mixture was evaporated to dryness; the residue was dissolved in a mixture of 500 mL water and 750 mL ethyl acetate. The organic phase was separated, washed with water (2x), saturated NaCl (2x) and was dried (Na₂SO₄). It was then evaporated to dryness to give the crude product as a yellow solid which was purified by filtering through 400 mL silica gel pad using toluene elution;Yield: 10.45g (73percent);¹H-NMR (CDCl₃): δ (ppm) 7.87 (d, 1H, J=8.7Hz), 7.51-7.46 (m, 2H), 2.61 (s, 3H).
73%	Stage #1: With hydrogen bromide; sodium nitrite In water; acetone at 0 - 5℃; for 0.166667 h; Stage #2: With copper(I) bromide In water; acetone at 15℃;	To an ice cold solution of 10.0 g (65.7 mmol) 3-methyl-4-nitro-phenylamine in 200 mL acetone, was added 21 mL (197.2 mmol) 48percent HBr. 4.54 g (65.7 mmol) NaNO₂ was dissolved in 20 mL water and was added dropwise to the amine solution at a rate to keep the temperature under 5° C. The mixture was stirred at this temperature for an additional 10 minutes then 1.5 g (10 mmol) solid CuBr was added portion-wise at a rate to keep the temperature under 15° C. The reaction was complete when no more nitrogen evaluated (about 15 minutes). The reaction mixture was evaporated to dryness; the residue was dissolved in a mixture of 500 mL water and 750 mL ethyl acetate. The organic phase was separated, washed with water (2), saturated NaCl (2) and was dried (Na₂SO₄). It was then evaporated to dryness to give the crude product as a yellow solid which was purified by filtering through 400 mL silica gel pad using toluene elution; Yield: 10.45 g (73percent); ¹H-NMR (CDCl₃): δ (ppm) 7.87 (d, 1H, J=8.7 Hz), 7.51-7.46 (m, 2H), 2.61 (s, 3H).
73%	Stage #1: With hydrogen bromide; sodium nitrite In water; acetone at 0 - 5℃; for 0.166667 h; Stage #2: With copper(I) bromide In water; acetone at 15℃; for 0.25 h;	To an ice cold solution of 10.0 g (65.7 mmol) 3-methyl-4-nitro-phenylamine in 200 mL acetone, was added 21 mL (197.2 mmol) 48percent HBr. 4.54g (65.7 mmol) NaNO₂ was dissolved in 20 mL water and was added dropwise to the amine solution at a rate to keep the temperature under 5 ⁰C. The mixture was stirred at this temperature for an additional 10 <n="96"/>minutes then 1.5 g (10 mmol) solid CuBr was added portion- wise at a rate to keep the temperature under 15 ⁰C. The reaction was complete when no more nitrogen evaluated (about 15 minutes). The reaction mixture was evaporated to dryness; the residue was dissolved in a mixture of 500 mL water and 750 mL ethyl acetate. The organic phase was separated, washed with water (2x), saturated NaCl (2x) and was dried (Na₂SO₄). It was then evaporated to dryness to give the crude product as a yellow solid which was purified by filtering through 400 mL silica gel pad using toluene elution;Yield: 10.45g (73percent);¹H-NMR (CDCl₃): δ (ppm) 7.87 (d, IH, J=8.7Hz), 7.51-7.46 (m, 2H), 2.61 (s, 3H).

Reference： [1] Patent: WO2006/76529, 2006, A1, . Location in patent: Page/Page column 92-93
[2] Patent: US2007/32488, 2007, A1, . Location in patent: Page/Page column 28-29
[3] Patent: WO2008/8912, 2008, A1, . Location in patent: Page/Page column 81; 94-95
[4] Journal of the American Chemical Society, 1948, vol. 70, p. 219
[5] Recueil des Travaux Chimiques des Pays-Bas, 1934, vol. 53, p. 1011,1016, 1025
[6] Journal of the Chemical Society, 1929, p. 1255

3
[ 583-75-5 ]
[ 52414-98-9 ]

Yield	Reaction Conditions	Operation in experiment
74%	With dihydrogen peroxide; trifluoroacetic anhydride In dichloromethane at 0℃; for 1.58333 h; Heating / reflux	Example 37; 2-methoxy-N-(2-methyl-4-(1-(2-(methylamino)ethyl)piperidin-4-yl)phenyl)benzamide (199); Step 1 4-bromo-2-methyl-1 -nitrobenzene (193); [0383] To a mixture of H₂O₂ (3 95 ml, 64 5 mmol) in DCM (32 0 ml) cooled at O ⁰C was added TFAA (10 93 ml, 77 mmol) and the mixture was stirred for 5 minutes at that temperature then the ice bath was removed and a reflux condenser was installed and a solution of 4-bromo-2-methylaniline (3 g, 16 12 mmol) in DCM (6 4 ml) was added drop-wise over approx 30 minutes The reaction was heated at reflux for an additional hour then it it was cooled, washed with 30 mL of water then 30 mL of sat NaHCO₃ and the organic layer was dried over MgSO₄ and concentrated under vacuum The crude material was purified by flash to afford 193 (2 57 g, 1 1 9 mmol, 74percent) ¹H NMR (CDCI₃) δ (ppm) 7 88 (d, J = 8 6 Hz, 1 H),7 53 (d, J = 2 2 Hz, 1 H), 7 49 (dd, J = 8 6, 2 2 Hz, 1 H), 2 60 (s, 3H)

Reference： [1] Patent: WO2008/104077, 2008, A1, . Location in patent: Page/Page column 122
[2] Journal of Organic Chemistry, 1955, vol. 20, p. 1458
[3] Patent: US4287201, 1981, A,

4
[ 611-23-4 ]
[ 52414-98-9 ]

Reference： [1] Organic Letters, 2015, vol. 17, # 24, p. 6210 - 6213

5
[ 591-17-3 ]
[ 52414-98-9 ]
[ 40385-54-4 ]

Reference： [1] Bulletin de la Societe Chimique de France, 1932, vol. <4> 51, p. 1416,1421

6
[ 108-44-1 ]
[ 52414-98-9 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1934, vol. 53, p. 1011,1016, 1025

7
[ 591-17-3 ]
[ 7697-37-2 ]
[ 108-39-4 ]
[ 52414-98-9 ]
[ 52414-97-8 ]
[ 40385-54-4 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1934, vol. 53, p. 1011,1016, 1025

8
[ 591-17-3 ]
[ 7697-37-2 ]
[ 52414-98-9 ]
[ 52414-97-8 ]
[ 40385-54-4 ]
[ 5411-53-0 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1934, vol. 53, p. 1011,1016, 1025

9
[ 591-17-3 ]
[ 7697-37-2 ]
[ 108-39-4 ]
[ 52414-98-9 ]
[ 52414-97-8 ]
[ 40385-54-4 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1934, vol. 53, p. 1011,1016, 1025

10
[ 591-17-3 ]
[ 7697-37-2 ]
[ 52414-98-9 ]
[ 52414-97-8 ]
[ 40385-54-4 ]
[ 5411-53-0 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1934, vol. 53, p. 1011,1016, 1025

11
[ 52414-98-9 ]
[ 35287-42-4 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1972, vol. 9, p. 119 - 122

12
[ 591-17-3 ]
[ 52414-98-9 ]
[ 40385-54-4 ]

Reference： [1] Bulletin de la Societe Chimique de France, 1932, vol. <4> 51, p. 1416,1421

13
[ 591-17-3 ]
[ 7697-37-2 ]
[ 108-39-4 ]
[ 52414-98-9 ]
[ 52414-97-8 ]
[ 40385-54-4 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1934, vol. 53, p. 1011,1016, 1025

14
[ 591-17-3 ]
[ 7697-37-2 ]
[ 52414-98-9 ]
[ 52414-97-8 ]
[ 40385-54-4 ]
[ 5411-53-0 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1934, vol. 53, p. 1011,1016, 1025

15
[ 52414-98-9 ]
[ 124840-61-5 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 2, p. 421 - 426

[ 52414-98-9 ] Synthesis Path-Downstream 1~88

1
[ 591-17-3 ]
[ 52414-98-9 ]
[ 40385-54-4 ]

Reference： [1]Bulletin de la Societe Chimique de France,1932,vol. <4> 51,p. 1416,1421

2
[ 52414-98-9 ]
[ 1124-31-8 ]
(3-methyl-4-nitro-phenyl)-(3-nitro-phenyl)-ether [ No CAS ]

Reference： [1]Journal of the Chemical Society,1934,p. 52,54

3
[ 52414-98-9 ]
[ 930-69-8 ]
[ 60326-45-6 ]

Reference： [1]Bulletin de la Societe Chimique de France,1932,vol. <4> 51,p. 1416,1421

4
[ 52414-98-9 ]
[ 88070-23-9 ]

Reference： [1]Journal of the Chemical Society,1932,p. 1987

5
[ 52414-98-9 ]
bis-(3-methyl-4-nitro-phenyl)-sulfide [ No CAS ]

Reference： [1]Journal of the Chemical Society,1934,p. 1140

6
[ 52414-98-9 ]
bis-(3-methyl-4-nitro-phenyl)-disulfide [ No CAS ]

Reference： [1]Journal of the Chemical Society,1934,p. 1140

7
[ 52414-98-9 ]
[ 583-75-5 ]

Yield	Reaction Conditions	Operation in experiment
	With 2 wt% Pd/C; hydrogen; at 120℃; under 7500.75 Torr;	Examples 27 to 34 investigated the effect of carbon-supported large-particle palladium catalysts on the synthesis of halogenated aromatic amines by solvent-free hydrogenation of different halogenated aromatic nitro compounds. In a 500 ml reactor, 200 g of different halogenated aromatic nitro compounds were added, 2 g of a 2 wt% palladium catalyst containing a large particle size in Example 5, shutting down the reactor; first with nitrogen replacement reactor inside the air three times, and then replaced with hydrogen three times, And then heated to 120 C, and the hydrogen pressure rose to 1MPa, open stirring to 1000r/min; to maintain the reaction temperature and pressure until the end of the reaction; cooling cooling, remove the reactor liquid, filter separation The catalyst was used and the water in the filtrate was separated by phase separation to give the desired product Halogenated aromatic amine. The reaction product was analyzed by gas chromatography. The results are shown in Table 4.

Reference： [1]Justus Liebigs Annalen der Chemie,1875,vol. 177,p. 246
[2]Justus Liebigs Annalen der Chemie,1875,vol. 177,p. 246
[3]Patent: CN104163764,2016,B .Location in patent: Paragraph 0050-0053

8
[ 611-05-2 ]
[ 52414-98-9 ]

Yield	Reaction Conditions	Operation in experiment
73%		Preparation of 4-bromo~2-methyI-1-nitro-benzene (102):[0190] To an ice cold solution of 10.0 g (65.7 mmol) 3-methyl-4-nitro-phenylamine in 200 niL acetone, was added 21 niL (197.2 mmol) 48% HBr. 4.54g (65.7 mmol) NaNO2 was dissolved in 20 mL water and was added dropwise to the amine solution at a rate to keep the temperature under 5 C. The mixture was stirred at this temperature for an additional 10 minutes then 1.5 g (10 mmol) solid CuBr was added portion-wise at a rate to keep the temperature under 15 C. The reaction was complete when no EPO <DP n="94"/>more nitrogen evaluated (about 15 minutes). The reaction mixture was evaporated to dryness; the residue was dissolved in a mixture of 500 mL water and 750 mL ethyl acetate. The organic phase was separated, washed with water (2x), saturated NaCl (2x) and was dried (Na2SO4). It was then evaporated to dryness to give the crude product as a yellow solid which was purified by filtering through 400 mL silica gel pad using toluene elution;Yield: 10.45g (73%);1H-NMR (CDCl3): delta (ppm) 7.87 (d, 1H, J=8.7Hz), 7.51-7.46 (m, 2H), 2.61 (s, 3H).
73%		To an ice cold solution of 10.0 g (65.7 mmol) 3-methyl-4-nitro-phenylamine in 200 mL acetone, was added 21 mL (197.2 mmol) 48% HBr. 4.54 g (65.7 mmol) NaNO2 was dissolved in 20 mL water and was added dropwise to the amine solution at a rate to keep the temperature under 5 C. The mixture was stirred at this temperature for an additional 10 minutes then 1.5 g (10 mmol) solid CuBr was added portion-wise at a rate to keep the temperature under 15 C. The reaction was complete when no more nitrogen evaluated (about 15 minutes). The reaction mixture was evaporated to dryness; the residue was dissolved in a mixture of 500 mL water and 750 mL ethyl acetate. The organic phase was separated, washed with water (2), saturated NaCl (2) and was dried (Na2SO4). It was then evaporated to dryness to give the crude product as a yellow solid which was purified by filtering through 400 mL silica gel pad using toluene elution; Yield: 10.45 g (73%); 1H-NMR (CDCl3): delta (ppm) 7.87 (d, 1H, J=8.7 Hz), 7.51-7.46 (m, 2H), 2.61 (s, 3H).
73%		To an ice cold solution of 10.0 g (65.7 mmol) 3-methyl-4-nitro-phenylamine in 200 mL acetone, was added 21 mL (197.2 mmol) 48% HBr. 4.54g (65.7 mmol) NaNO2 was dissolved in 20 mL water and was added dropwise to the amine solution at a rate to keep the temperature under 5 0C. The mixture was stirred at this temperature for an additional 10 <n="96"/>minutes then 1.5 g (10 mmol) solid CuBr was added portion- wise at a rate to keep the temperature under 15 0C. The reaction was complete when no more nitrogen evaluated (about 15 minutes). The reaction mixture was evaporated to dryness; the residue was dissolved in a mixture of 500 mL water and 750 mL ethyl acetate. The organic phase was separated, washed with water (2x), saturated NaCl (2x) and was dried (Na2SO4). It was then evaporated to dryness to give the crude product as a yellow solid which was purified by filtering through 400 mL silica gel pad using toluene elution;Yield: 10.45g (73%);1H-NMR (CDCl3): delta (ppm) 7.87 (d, IH, J=8.7Hz), 7.51-7.46 (m, 2H), 2.61 (s, 3H).

Reference： [1]Mendeleev Communications,2018,vol. 28,p. 261 - 263
[2]Patent: WO2006/76529,2006,A1 .Location in patent: Page/Page column 92-93
[3]Patent: US2007/32488,2007,A1 .Location in patent: Page/Page column 28-29
[4]Patent: WO2008/8912,2008,A1 .Location in patent: Page/Page column 81; 94-95
[5]Journal of the American Chemical Society,1948,vol. 70,p. 219
[6]Journal of the Chemical Society,1929,p. 1255

9
[ 52414-98-9 ]
[ 4637-24-5 ]
[ 105205-48-9 ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide; at 145℃; for 2h;	Preparation of [(E)-2-(5-bromo-2-nitro-phenyl)-viny1]-dimethyI-amine (104): [0191] A mixture of 9.26 g (42.9 mmol) of compound 102, 14.3 mL (107.2 mmol) N,N-dimethylformamide dimethylacetal and 11 mL DMF was heated under a slow argon flow at 145 C (bath) for two hours. The reaction mixture was then evaporated to dryness. The dark pink product crystallized upon standing; MS: 271.01 & 273.01 (M+-H+); 1H-NMR (DMSO-d6): delta (ppm) 7.88 (d, 1H), 7.68 (dd, 1H), 7.58 (d, 1H), 7.05 (d, 1H), 5.59 (d, 1H), 2.90 (s, 6H).
	In N,N-dimethyl-formamide; at 145℃; for 2h;	Preparation of [(E)-2-(5-bromo-2-nitro-phenyl)-vinyl]-dimethyl-amine 7.4: A mixture of 9.26 g (42.9 mmol) of compound 7.2, 14.3 mL (107.2 mmol) N,N-dimethylformamide dimethylacetal 7.3 and 11 mL DMF was heated under a slow argon flow at 145 C. (bath) for two hours. The reaction mixture was then evaporated to dryness. The dark pink product crystallized upon standing; MS: 271.01 & 273.01 (M+H+); 1H-NMR (DMSO-d6): delta (ppm) 7.88 (d, 1H), 7.68 (dd, 1H), 7.58 (d, 1H), 7.05 (d, 1H), 5.59 (d, 1H), 2.90 (s, 6H).
	In N,N-dimethyl-formamide; at 145℃; for 2h;	A mixture of 9.26 g (42.9 mmol) of compound 4.2, 14.3 mL (107.2 mmol) N,N- dimethylformamide dimethylacetal 4.3 and 11 mL DMF was heated under a slow argon flow at 145 0C (bath) for two hours. The reaction mixture was then evaporated to dryness. The dark pink product crystallized upon standing; MS: 271.01 & 273.01 (M+H+); 1H-NMR (DMSO-de): delta (ppm) 7.88 (d, IH), 7.68 (dd, IH), 7.58 (d, IH), 7.05 (d, IH), 5.59 (d, IH), 2.90 (s, 6H).

Reference： [1]Journal of Organic Chemistry,1986,vol. 51,p. 5106 - 5110
[2]Patent: WO2006/76529,2006,A1 .Location in patent: Page/Page column 92; 93
[3]Patent: US2007/32488,2007,A1 .Location in patent: Page/Page column 28-29
[4]Patent: WO2008/8912,2008,A1 .Location in patent: Page/Page column 81; 95

10
[ 52414-98-9 ]
[ 35287-42-4 ]

Reference： [1]Journal of Heterocyclic Chemistry,1972,vol. 9,p. 119 - 122

11
[ 52414-98-9 ]
[ 95-92-1 ]
[ 17403-17-7 ]

Reference： [1]Journal of the Chemical Society C: Organic,1968,p. 504 - 507

12
[ 52414-98-9 ]
[ 10486-08-5 ]
[ 53258-92-7 ]

Reference： [1]Gazzetta Chimica Italiana,1973,vol. 103,p. 723 - 730
[2]Gazzetta Chimica Italiana,1973,vol. 103,p. 723 - 730

13
[ 591-17-3 ]
[ 7697-37-2 ]
[ 108-39-4 ]
[ 52414-98-9 ]
[ 52414-97-8 ]
[ 40385-54-4 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1934,vol. 53,p. 1011,1016, 1025

14
[ 591-17-3 ]
[ 7697-37-2 ]
[ 52414-98-9 ]
[ 52414-97-8 ]
[ 40385-54-4 ]
[ 5411-53-0 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1934,vol. 53,p. 1011,1016, 1025

16
[ 52414-98-9 ]
[ 108-59-8 ]
4-(5-bromo-2-nitro-phenyl)-3-oxo-butyric acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 421 - 426

17
[ 52414-98-9 ]
[ 4637-24-5 ]
[ 583-75-5 ]
[ 105205-48-9 ]

Yield	Reaction Conditions	Operation in experiment
	With pyrrolidine; In N,N-dimethyl-formamide; at 110℃; for 1.5h;	4-Bromo-2-(2,2-dimethoxyethyl)-1-nitrobenzene (66): Compound 64 (500 mg, 2.315 mmol) (Olsen et al., U.S. Pat. No. 4,287,201) was dissolved in anhydrous dimethylformamide (10 mL) in a dry argon purged flask fitted with a magnetic stir bar and condenser. Dimethylformamide dimethylacetal (828 mg, 6.945 mmol) and pyrrolidine (165 mg, 2.315 mmol) are added to the flask and mixture heated 110 C. for 90 minutes. After cooling to room temperature, the reaction mixture was diluted with diethyl ether and H2O, transferred to a separatory funnel and the organic layer collected. The organic layer washed with H2O (twice) and the combined aqueous layers back extracted with diethyl ether (twice). The combined organic layers were dried over anhydrous sodium sulphate, filtered, concentrated to yield a dark red oil, 65, which is utilized without purification. The crude enamine is dissolved in anhydrous methanol, treated with chlorotrimethylsilane (3 equivalents) and refluxed for 20 hours. The reaction was concentrated under reduced pressure and the residue was partitioned between a saturated sodium bicarbonate solution and ethyl acetate. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulphate, filtered, concentrated and the residue purified via chromatography on silica gel (EtOAc:Hexanes, 1:9) to yield a pale brown solid, 66 (330 mg, 49.2%). 1H NMR (CDCl3) delta 3.20 (d, 2H, J=5.2 Hz), 3.35 (s, 6H), 4.55 (t, 1H, J=5.2 Hz), 7.51 (dd, 1H, J=8.5, 2.1 Hz), 7.58 (d, 1H, J=1.9 Hz), 7.78 (d, 1H, J=8.6 Hz); ESI-MS (m/z, %): 312/314 (M+Na+, 90%), 198/200 (100%); ESI-HRMS calculated for C10H12NO4NaBr (M+Na+), calculated: 311.9841; observed: 311.9826.

Reference： [1]Patent: US2007/254940,2007,A1 .Location in patent: Page/Page column 51-52

18
[ 52414-98-9 ]
[ 276884-13-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 421 - 426

19
[ 52414-98-9 ]
5-Bromo-3-[1-(2,3-dimethoxy-phenyl)-meth-(Z)-ylidene]-1,3-dihydro-indol-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 421 - 426

20
[ 52414-98-9 ]
[ 856435-10-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 421 - 426

21
[ 52414-98-9 ]
5-Bromo-3-[1-(7-methyl-1H-indol-3-yl)-meth-(Z)-ylidene]-1,3-dihydro-indol-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 421 - 426

22
[ 52414-98-9 ]
(3Z)-5-(4-hydroxy-3-methoxyphenyl)-3-(1H-pyrrol-2-ylmethylene)-1,3-dihydro-2H-indol-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 421 - 426

23
[ 52414-98-9 ]
3-[1-(2,3-Dimethoxy-phenyl)-meth-(Z)-ylidene]-5-(4-hydroxy-3-methoxy-phenyl)-1,3-dihydro-indol-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 421 - 426

24
[ 52414-98-9 ]
5-(4-Hydroxy-3-methoxy-phenyl)-3-[1-(1H-indol-3-yl)-meth-(Z)-ylidene]-1,3-dihydro-indol-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 421 - 426

25
[ 52414-98-9 ]
5-(4-Hydroxy-3-methoxy-phenyl)-3-[1-(7-methyl-1H-indol-3-yl)-meth-(Z)-ylidene]-1,3-dihydro-indol-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 421 - 426

26
[ 52414-98-9 ]
[ 20870-78-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 421 - 426

27
[ 52414-98-9 ]
[ 10075-50-0 ]

Reference： [1]Journal of Organic Chemistry,1986,vol. 51,p. 5106 - 5110

28
[ 52414-98-9 ]
[ 1196-69-6 ]

Reference： [1]Journal of Organic Chemistry,1986,vol. 51,p. 5106 - 5110

29
[ 52414-98-9 ]
[ 105205-51-4 ]

Reference： [1]Journal of Organic Chemistry,1986,vol. 51,p. 5106 - 5110

30
[ 108-44-1 ]
[ 52414-98-9 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1934,vol. 53,p. 1011,1016, 1025

31
[ 52414-98-9 ]
[ 34237-94-0 ]

Reference： [1]Journal of the Chemical Society,1934,p. 1140

32
[ 52414-98-9 ]
acetic acid-[2-methyl-4-(3-methyl-4-nitro-phenylsulfanyl)-anilide] [ No CAS ]

Reference： [1]Journal of the Chemical Society,1934,p. 1140

33
[ 52414-98-9 ]
bis-(4-acetylamino-3-methyl-phenyl)-sulfide [ No CAS ]

Reference： [1]Journal of the Chemical Society,1934,p. 1140

34
[ 52414-98-9 ]
benzoic acid-[2-methyl-4-(3-methyl-4-nitro-phenylsulfanyl)-anilide] [ No CAS ]

Reference： [1]Journal of the Chemical Society,1934,p. 1140

35
[ 52414-98-9 ]
bis-(4-benzoylamino-3-methyl-phenyl)-sulfide [ No CAS ]

Reference： [1]Journal of the Chemical Society,1934,p. 1140

36
[ 52414-98-9 ]
[ 35287-31-1 ]

Reference： [1]Journal of Heterocyclic Chemistry,1972,vol. 9,p. 119 - 122

37
[ 52414-98-9 ]
[ 35287-28-6 ]

Reference： [1]Journal of Heterocyclic Chemistry,1972,vol. 9,p. 119 - 122

38
[ 52414-98-9 ]
2-Acetamid-2-(5-brom-2-nitrobenzyl)-malonsaeureaethylester [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,1972,vol. 9,p. 119 - 122

39
[ 52414-98-9 ]
[ 60326-45-6 ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide; thiophenol;	Step B: Preparation of 2-nitro-5-phenylthiotoluene To a suspension of sodium hydride (57% oil emulsion, 1.11 g) in dimethylformamide (30 ml) is added in small portions 2.48 ml (2.64 g, 24 mmoles) of thiophenol. The mixture is cooled in an ice bath while a solution of <strong>[52414-98-9]5-bromo-2-nitrotoluene</strong> (4.32 g, 20 mmoles) in dimethylformamide (10 ml) is added dropwise. The mixture is stirred for an additional 30 minutes and then poured into ice water (200 ml). The partially crystalline product is extracted with dichloromethane and the combined extracts are washed with water and dried. The solvents are evaporated under high vacuum to remove DMF and the residue is covered with hexane. The resultant crystals are broken up and filtered to give pure product, 2-nitro-5-phenylthiotoluene, 3.78 g, m.p. 69-75.

Reference： [1]Patent: US4287201,1981,A

40
[ 52414-98-9 ]
[ 81290-20-2 ]
[ 67192-42-1 ]

Reference： [1]Chemical Communications,2011,vol. 47,p. 7236 - 7238

41
[ 52414-98-9 ]
C₂₁H₂₄N₄S*2ClH [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5301 - 5304

42
[ 52414-98-9 ]
C₂₀H₂₂N₄S*2ClH [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5301 - 5304

43
[ 52414-98-9 ]
N-(1-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-1H-indol-5-yl)thiophene-2-carboximidamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5301 - 5304

44
[ 52414-98-9 ]
N-(1-(Quinuclidin-3-yl)-1H-indol-5-yl)thiophene-2-carboximidamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5301 - 5304

45
[ 52414-98-9 ]
[ 954386-98-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5301 - 5304

46
[ 52414-98-9 ]
N-(4-Bromo-2-(2,2-dimethoxyethyl)phenyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-amine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5301 - 5304

47
[ 52414-98-9 ]
[ 954387-00-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5301 - 5304

48
[ 52414-98-9 ]
5-Bromo-1-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-1H-indole [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5301 - 5304

49
[ 52414-98-9 ]
[ 954387-01-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5301 - 5304

50
[ 52414-98-9 ]
[ 954386-99-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5301 - 5304

51
[ 52414-98-9 ]
1-(8-Methyl-8-azabicyclo[3.2.1]octan-3-yl)-1H-indol-5-amine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5301 - 5304

52
[ 52414-98-9 ]
[ 954387-02-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5301 - 5304

53
[ 52414-98-9 ]
[ 4637-24-5 ]
[ 105205-48-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5301 - 5304

54
[ 52414-98-9 ]
[ 1606982-19-7 ]
[ 1606982-20-0 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 2606 - 2609

55
[ 52414-98-9 ]
[ 74-89-5 ]
[ 52177-10-3 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 2606 - 2609

56
[ 52414-98-9 ]
C₁₁H₁₇NO [ No CAS ]

Reference： [1]Patent: WO2014/145022,2014,A1

57
[ 52414-98-9 ]
C₁₁H₁₅IO [ No CAS ]

Reference： [1]Patent: WO2014/145022,2014,A1

58
[ 52414-98-9 ]
C₁₉H₁₉N₃O [ No CAS ]

Reference： [1]Patent: WO2014/145022,2014,A1

59
[ 52414-98-9 ]
C₁₉H₁₈BrN₃ [ No CAS ]

Reference： [1]Patent: WO2014/145022,2014,A1

60
[ 52414-98-9 ]
C₃₁H₂₇ClN₆O₂ [ No CAS ]

Reference： [1]Patent: WO2014/145022,2014,A1

61
[ 52414-98-9 ]
[ 927-74-2 ]
C₁₁H₁₁NO₃ [ No CAS ]

Reference： [1]Patent: WO2014/145022,2014,A1 .Location in patent: Page/Page column 54

62
[ 52414-98-9 ]
1-methyl-4-((3'-methyl-4'-nitro-[1,1'-biphenyl]-4-yl)oxy)piperidine [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 89,p. 442 - 466

63
[ 52414-98-9 ]
3',6-dimethoxy-N-(3-methyl-4'-((1-methylpiperidin-4-yl)oxy)-[1,1'-biphenyl]-4-yl)-[1,1'-biphenyl]-3-carboxamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 89,p. 442 - 466

64
[ 52414-98-9 ]
C₁₉H₂₄N₂O [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 89,p. 442 - 466

65
[ 52414-98-9 ]
[ 71597-85-8 ]
3'-methyl-4'-nitro-[1,1'-biphenyl]-4-ol [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 89,p. 442 - 466

66
[ 611-23-4 ]
[ 52414-98-9 ]

Reference： [1]Organic Letters,2015,vol. 17,p. 6210 - 6213

67
[ 52414-98-9 ]
rac-ethyl 1-(6-(3-((4-(1-(cyclopropanecarbonyl)piperidin-4-yl)-2-methylphenyl)-amino)-2,3-dihydro-1H-inden-4-yl)pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate [ No CAS ]