Name: 66584-32-5|3-Bromo-N-methylaniline|98%
Brand: Ambeed
SKU: A229344
Price: 5.0 USD
Availability: InStock
Rating: 92 (25 reviews)

1
[ 66584-32-5 ]
[ 160964-30-7 ]
[ 173847-46-6 ]

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,1995,vol. 106,p. 105 - 114

2
[ 66584-32-5 ]
[ 215433-49-1 ]
3,3'-bis(3-N-methylaminophenyl)-2,2'-dimethoxy-1,1'-binaphthyl [ No CAS ]

Reference： [1]Monatshefte fur Chemie,1998,vol. 129,p. 1319 - 1327

3
[ 126799-86-8 ]
[ 66584-32-5 ]

Reference： [1]Tetrahedron Letters,1999,vol. 40,p. 2071 - 2074

4
[ 66584-32-5 ]
C₂₁H₂₁N₃ [ No CAS ]
C₂₈H₂₈N₄ [ No CAS ]
C₃₅H₃₅N₅ [ No CAS ]
C₄₂H₄₂N₆ [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1999,vol. 64,p. 8236 - 8241

5
[ 66584-32-5 ]
C₂₈H₂₈N₄ [ No CAS ]
C₃₅H₃₅N₅ [ No CAS ]
C₄₉H₄₉N₇ [ No CAS ]
C₅₆H₅₆N₈ [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1999,vol. 64,p. 8236 - 8241

6
[ 252936-78-0 ]
[ 66584-32-5 ]

Reference： [1]Journal of Organic Chemistry,1999,vol. 64,p. 8236 - 8241

7
[ 66584-32-5 ]
[ 3355-28-0 ]
[ 411242-56-3 ]

Reference： [1]European Journal of Organic Chemistry,2002,p. 39 - 48

8
[ 833451-74-4 ]
[ 66584-32-5 ]
(3-bromo-phenyl)-(7,8-dimethoxy-10,11-dihydro-5-thia-2,4,11-triazadibenzo[a,d]cyclohepten-1-yl)-methyl-amine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 9629 - 9631
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5102 - 5106

9
[ 66584-32-5 ]
[ 36763-49-2 ]
(3-bromo-phenyl)-methyl-(4-p-tolyloxy-but-2-ynyl)-amine [ No CAS ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2006,vol. 45,p. 719 - 725

10
[ 66584-32-5 ]
[ 106-95-6 ]
[ 373623-22-4 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium carbonate; In acetonitrile; at 90℃;	Compound 6 was synthesized in accordance with the following scheme. Potassium carbonate (7.46 g, 54.0 mmol, 2.0 eq.) was suspended in acetonitrile (20 mE), 3-bromo-N-methyl- aniline (4.96 g, 26.7 mmol, 1 eq.) and allyl bromide (3.87 g, 31.3 mmol, 1.2 eq.) were added, and the mixture was heated and refluxed overnight at 90 C. while being stirred. The reaction mixture was filtered through celite, the filtration residue and celite were then washed using ethyl acetate, and the solvent was removed under reduced pressure from a mixture of filtrate and washing solution. The resulting residue was purified by medium-pressure silica gel chromatography (eluent n-hexane/ethyl acetate=100/0 to 98/2) toobtain the objective compound 6 (5.98 g, 99%). 1H NMR (400 MHz, CDCl3): δ 2.95 (s, 3H),3.91-3.93 (m, 2H), 5.15-5.21 (m, 2H), 5.79-5.89 (m, 1H),6.63-6.65 (m, 1H), 6.82-6.86 (m, 2H), 7.06-7.10 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 38.1, 55.0, 110.9, 115.0,116.4, 119.1, 123.5, 130.4, 133.1, 150.7; HRMS (ESIj:Calcd for [M+H], 226.02259, Found, 226.02210 (-0.5 mmu).
73%	With potassium carbonate; In acetonitrile; at 80℃;	<strong>[66584-32-5]N-methyl-3-bromoaniline</strong> (2.27 g, 12.2 mmol), K2CO3 (4.20 g, 30.4 mol), and allyl bromide (4.00 g, 33.1 mmol) were dissolved in MeCN (50 mL) and stirred overnight at 80 C. After cooling to room temperature and filtering, the solvent of the filtrate was removed under reduced pressure. The remaining oil droplets were purified by silica gel column chromatography (CH2Cl2/n-hexane=), and N-allyl-<strong>[66584-32-5]N-methyl-3-bromoaniline</strong> was obtained (2.02 g, 8.94 mol, yield 73%). (0243) 1H NMR (300 MHz, CDCl3): δ=2.93 (s, 3H), 3.89-3.91 (m, 2H), 5.10-5.18 (m, 2H), 5.74-5.87 (m, 1H), 6.60 (dd, J=8.4 Hz, 2.6 Hz, 1H), 6.78-6.81 (m 2H), 7.05 (m, 1H). 13C NMR (100 MHz, CDCl3): δ=38.1, 55.1, 110.9, 115.0, 116.5, 119.1, 123.5, 130.4, 133.1, 150.7
72%	With sodium carbonate; In tetrahydrofuran;Reflux;	[Synthesis of Compound J5] (0194) Compound J4 (5.00 g, 26.9 mmol, 1 Eq) was dissolved in tetrahydrofuran (50 mL). Next, sodium carbonate (7.85 g, 56.9 mmol, 2.1 Eq) and allyl bromide (3.5 mL, 40.3 mmol, 1.5 Eq) were added and heated and refluxed overnight. More allyl bromide (3.5 mL, 40.3 mmol, 1.5 Eq) was added and heated and refluxed for two days. After air-cooling, the reaction solution was separated by filtration, and the filtrate was concentrated. The residue obtained was separated and purified by silica gel column chromatography (eluent: hexane/ethyl acetate=100/0 to 90/10), and compound J5 (5.53 g, 72%) was obtained as a colorless, transparent liquid. (0195) 1H NMR (CDCl3): δ 7.05 (t, J=8.1 Hz, 1H), 6.83-6.79 (m, 2H), 6.61 (dd, J=8.4 Hz, 2.2 Hz, 1H), 5.81 (ddt, J=17.0 Hz, 10.4 Hz, 4.9 Hz, 1H), 5.16 (dq, J=10.4 Hz, 1.6 Hz, 1H), 5.14 (dq, J=17.0 Hz, 1.6 Hz, 1H), 3.90 (dt, J=4.9 Hz, 1.6 Hz, 2H), 2.93 (s, 3H).; 13C NMR (CDCl3): δ 150.7 (C), 133.1 (CH), 130.4 (CH), 123.5 (C), 119.1 (CH), 116.5 (CH2), 115.1 (CH), 111.0 (CH), 55.1 (CH2), 38.2 (CH2); HRMS-ESI (m/z): [M+H]+ calcd for C10H13NBrN: 226.02259. found: 226.02478 (-2.2 mDa, -9.7 ppm).

Reference： [1]Patent: US2018/52109,2018,A1 .Location in patent: Paragraph 0089; 0090; 0091; 0092
[2]Journal of the American Chemical Society,2020,vol. 142,p. 9625 - 9633
[3]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2006,vol. 45,p. 719 - 725
[4]Patent: US2020/87326,2020,A1 .Location in patent: Paragraph 0242-0243
[5]Patent: US2017/45525,2017,A1 .Location in patent: Paragraph 0193; 0194; 0195

11
[ 591-19-5 ]
[ 74-88-4 ]
[ 66584-32-5 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 72h;Inert atmosphere;	[00488] KOH (179 mg, 3.20 mmol) and Mel (0.18 mL, 2.91 mmol) were sequentially added to a stirred solution of intermediate 31.1 (0.32 mL, 2.91 mmol) in DMF (3 mL) and magnetic stirring was continued for 3 days at r.t. The mixture was poured into H2O (50 mL) and extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with H2O (50 mL) and brine (50 mL), dried over anhydrous Na2S04, and evaporated to dryness. After purification by flash chromatography (PET/EtOAc, from 100% PET to 8:2 v/v PET/EtOAc), the title intermediate 35.1 (275 mg, 1.48 mmol) was obtained. Yield: 91%. MS-ESI(+) m/z: 185.9, 187.9 (M+H).
45%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2h;Heating;	To a mixture of 3-bromoaniline (5.00 g, 29.1 mmol), K2CO3 (12.1 g, 87.2 mmol), and DMF (10 mL), iodomethane (4.95 g, 34.9 mmol) was added, and the resulting mixture was stirred at 60C for 2 hours with heating. Water (30 mL) was added to the reaction mixture, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (ethyl acetate:hexane = 1:3) (Rf value, 0.44) to give N-methyl-3-bromoaniline (2.45 g, 13.1 mmol, yield 45%). 1H-NMR Spectrum (300MHz, CDCl3): δ (ppm): 2.82 (3H, s), 3.78 (1H, br), 6.51 (1H, d, J=8.1Hz), 6.73 (1H, s), 6.81 (1H, d, J=8.1Hz), 7.00 (1H, t, J=8.1Hz) .
	With potassium hydroxide; In DMF (N,N-dimethyl-formamide); at 20℃; for 20h;	2g (11.6 MMOL) 3-BROMOANILINE is dissolved in 15 mL DMF and treated with 716 mg (1.1 eq. ) KOH and 0.722 mL (1 eq. ) iodomethane under continuous stirring at room temperature for 20 hours. The reaction mixture is extracted with ethyl acetate and water, the combined organic phases are washed with brine and dried with sodium sulfate and evaporated to dryness. The residue is column chromatographed (ethyl acetate/petroleum ether 2: 5) to yield after evaporation the desired product as a yellow oil.

Reference： [1]Patent: WO2021/170658,2021,A1 .Location in patent: Paragraph 00488
[2]Patent: EP2987787,2016,A1 .Location in patent: Paragraph 0121
[3]Angewandte Chemie - International Edition,2016,vol. 55,p. 2810 - 2814
Angew. Chem.,2016,vol. 128,p. 2860 - 2864,5
[4]Patent: WO2004/87684,2004,A1 .Location in patent: Page 8-9
[5]Journal of Organic Chemistry,2022,vol. 87,p. 4965 - 4970

12
[ 64-18-6 ]
[ 66584-32-5 ]
[ 502925-17-9 ]

Yield	Reaction Conditions	Operation in experiment
	for 3h;Heating / reflux;	A solution of 3-bromo-N-methyl aniline (made as described by Lopez et al. in Tet. Lett., 1999,40, 11, p2071-2074 incorporated herein by reference; 7.4g, 39. 5mmol) in formic acid (20mL) was refluxed for 3h. The reaction mixture was then cooled to ambient temperature, diluted with water and extracted with diethyl ether. The organic phase was washed with saturated, aqueous sodium bicarbonate solution, water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a dark brown oil.
	for 3h;Heating / reflux;	N-f(3-Bromo-phenyl)-N-methyl-formamide (Intermediate 112); A solution of 3-bromo-N-methyl aniline (made as described by Lopez et al. in Tet. Lett., 1999,40, 11, p2071-2074 incorporated herein by reference; 7.4g, 39. 5mmol) in formic acid (20mL) was refluxed for 3h. The reaction mixture was then cooled to ambient temperature, diluted with water and extracted with diethyl ether. The organic phase was washed with saturated, aqueous sodium bicarbonate solution, water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a dark brown oil.

Reference： [1]Patent: WO2005/58301,2005,A1 .Location in patent: Page/Page column 176-177
[2]Patent: WO2005/58798,2005,A2 .Location in patent: Page/Page column 138

13
[ 66584-32-5 ]
[ 73183-34-3 ]
[ 869090-08-4 ]

Yield	Reaction Conditions	Operation in experiment
73 - 92%	With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 20 - 100℃; for 3 - 18h;Product distribution / selectivity;	Example 10Synthesis of (Z)-2-ethoxy-3-[3'-(1-methyl-3-phenethylureido)biphenyl-4-yl]acrylic acid a-Methyl[3-(4,4,5,5-tetramethyl[1.3.2]dioxaborolan-2-yl)phenyl]amineTo a solution of 10.9 g (59 mmol) of (3-bromophenyl)methylamine and 15 g (59 mmol) of bis-pinacoldiborane in 110 mL of dimethylformamide are added 17.4 g (177 mmol) of potassium acetate and 2.4 g (3 mmol) of dichloro[111'-bis(diphenylphosphino)ferrocene]palladium. The reaction medium is heated at 85 C. for 3 hours, cooled and extracted with dichloromethane. The organic phase is washed with water, dried over magnesium sulfate, filtered and evaporated. The residue obtained is purified by chromatography on a column of silica eluted with an 80/20 heptane/ethyl acetate mixture. 12.7 g (92%) of methyl[3-(4,4,5,5-tetramethyl[1.3.2]dioxaborolan-2-yl)phenyl]amine are obtained.; Example 28Synthesis of (Z)-3-[2-butoxy-3'-(3-butyl-1-methylureido)biphenyl-4-yl]-2-methoxyacrylic acid a-Methyl [3-(4,4,5,5-tetramethyl [1.3.2]dioxaborolan-2-yl)phenyl]amine35 g (4 mol %) of diphenylphosphinoferrocenepalladium dichloride are added to a solution of 200 g (1 mol) of (3-bromophenyl)methylamine prepared as described in Example 24f and 287 g (1.1 mol) of bis-pinacoldiborane in 21 of dimethylformamide in the presence of 316 g (3.2 mol) of potassium acetate. The reaction medium is heated at 100 C. for 3 hours and then stirred at room temperature for 15 hours. The reaction medium is filtered through Celite and 21 of ethyl acetate are then added to the filtrate. The organic medium is washed with water and the phases are then separated by settling. The solvents are evaporated off and the black oil obtained is purified by chromatography on silica gel eluted with a heptane/ethyl acetate mixture (90/10). 183 g (73%) of methyl[3-(4,4,5,5-tetramethyl[1.3.2]dioxaborolan-2-yl)phenyl]amine are obtained in the form of an orange-yellow oil.
73%	With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 20 - 100℃; for 18h;	35 g (4 mol%) of diphenylphosphinoferrocene-palladium dichloride are added to a solution of 200 g (1.075 mol, 1 eq) of (3-bromophenyl)methylamine and 286.7 g (1.129 mol, 1.05 eq) of pinacol diborane in 2 L of dimethylformamide in the presence of 316.4 g (3.225 mol, 3 eq) of potassium acetate. The reaction medium is heated at 100C for 3 hours and then stirred at room temperature for 15 hours. The reaction medium is filtered through Celite and 2 L of ethyl acetate are then added to the filtrate. The organic medium is washed with water and then separated out by settling. The solvents are evaporated off and the black oil obtained is chromatographed on silica gel eluted with heptane/ethyl acetate (90/10). 183 g of methyl-[3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]amine in the form of an orange-yellow oil are obtained. Yield = 73%
57%	With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In DMF (N,N-dimethyl-formamide); at 90℃; for 2h;	890 mg (3.5 mmol) of pinacolborane are added to a mixture of 600 mg (3.2 mmol) of <strong>[66584-32-5]3-bromo-N-methylaniline</strong> and 1 g (10.2 mmol) of potassium acetate in the presence of 130 mg (0.16 mmol, 5 mol%) of palladium dichloride diphenylphosphinopropane ferrocene (PdCl2dppf) in 10 ml of dimethylformamide. The mixture is stirred at 90C for 2 hours. The reaction is halted by the addition of 20 ml of water and then extraction is carried out with ethyl acetate. The organic phases are combined and dried over sodium sulphate. The solvents are evaporated and then the residue is chromatographed on silica gel (heptane/ethyl acetate 80/20). 420 mg of methyl[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amine are obtained in the form of an oil. Yield = 57%.

34%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 100℃; for 60h;	[00146] A suspension of <strong>[66584-32-5]3-bromo-N-methylaniline</strong> (500 mg, 2.69 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1 ,3,2-dioxaborolane) (751 mg, 2.96 mmol), PdCl2(dppf).CH2Cl2 adduct (219 mg, 0.269 mmol) and potassium acetate (317 mg, 3.22 mmol) in 1 ,4-Dioxane (10 mL) was stirred at 100 C for 60 h. The mixture was purified by silica column to afford the title compound (220 mg, 34%) as a brown oil. 1H-NMR (400 MHz, DMSO-c/6) δ ppm 7.07 (t, 1 H), 6.82 - 6.88 (m, 2H), 6.63 (d, 1 H), 5.57 (q, 1 H), 2.65 (s, 1 H), 1 .29 (s, 12H). [M+H]+ = 234.2.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4 dimethylcyclohexane; at 100℃;Inert atmosphere; Sealed tube;	A mixture of <strong>[66584-32-5]3-bromo-N-methylaniline</strong> (500 mg, 2.69 mmol), PdCl2(dppf)-CH2Cl2 (219 mg, 0.269 mmol), potassium acetate (791 mg, 8.06 mmol) and 4,4,4',4',5,5,5',5'- octamethyl-2,2'-bi(l,3,2-dioxaborolane) (955 mg, 3.76 mmol) in dioxane (8.0 mL) was purged with argon for 5 minutes. The reaction vessel was sealed and then heated at 100 C overnight. The reaction mixture was filtered through Celite and rinsed with ethyl acetate. The reaction solution was concentrated under reduced pressure and the residue was purified by chromatography on silica eluting with 0-50% ethyl acetate/hexane togive N-methyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)aniline. LRMS (ESI) calc'd for C)3H2iBN02 [M+H]+: 234, found 234.

Reference： [1]Patent: US2009/12129,2009,A1 .Location in patent: Page/Page column 17; 28; 39-40
[2]Patent: WO2006/18326,2006,A1 .Location in patent: Page/Page column 27
[3]Patent: WO2005/108352,2005,A1 .Location in patent: Page/Page column 35
[4]Patent: WO2017/149463,2017,A1 .Location in patent: Paragraph 00146
[5]Patent: WO2013/85802,2013,A1 .Location in patent: Page/Page column 119-120

14
[ 57598-34-2 ]
[ 66584-32-5 ]

Yield	Reaction Conditions	Operation in experiment
100%		f-(3-bromophenyl)methylamine150 g (500 mmol) of tert-butyl (3-bromophenyl)-N-methylcarbamate are placed in 600 mL of dichloromethane and 383 mL (5 mol) of trifluoroacetic acid. The reaction medium is stirred at room temperature for 24 hours, and then treated with saturated aqueous sodium carbonate solution and extracted with dichloromethane. The organic phase is washed with water, dried over magnesium sulfate, filtered and evaporated. 99 g (100%) of (3-bromophenyl)methylamine are obtained.
100%		3-Bromophenyl)methylamine is prepared as follows:150 g (500 mmol) of tert-butyl (3-bromophenyl)-N-methylcarbamate are placed in 600 ml of dichloromethane and 383 ml (5 mol) of trifluoroacetic acid. The reaction medium is stirred at ambient temperature for 24 hours, then treated with a saturated aqueous sodium carbonate solution and extracted with dichloromethane. The organic phase is washed with water, dried over magnesium sulphate, filtered and evaporated. 99 g (100%) of (3-bromophenyl)methylamine are obtained.
90%		Example 5Synthesis of (E)-3-[3'-(3-heptyl-1-methylureido)biphenyl-4-yl]-2-methylacrylic acid a-(3-bromophenyl)methylamine3.6 g (12.7 mmol) of tert-butyl 3-bromophenyl-N-methylcarbamate, prepared in a manner similar to that of Example 4b, are dissolved in 15 mL of dichloromethane. 5 mL of trifluoroacetic acid are added and the reaction mixture is stirred for 1 hour at room temperature. The reaction is worked up by addition of 50 mL of saturated sodium hydrogen carbonate solution and extraction with ethyl acetate. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated off and the residue is then purified by chromatography on a column of silica eluted with a 50/50 heptane/ethyl acetate mixture. 2.14 g (90%) of (3-bromophenyl)methylamine are obtained in the form of an oil.

90%		5 ml_ of trifluoromethanesulfonic acid are added to a solution of 3.6 g (12.7 mmol) of (3- tert-butyl bromophenyl)-A/-methylcarbamate in 15 mL of dichloromethane. The reaction medium is stirred for 1 hour at room temperature (r.t.). The reaction is stopped by addition of 50 mL of saturated sodium hydrogen carbonate solution and then extracted with ethyl acetate. The solvents are evaporated off and the residue is then chromatographed on silica gel. Eluent (1/1 heptane/ethyl acetate). 2.14 g of oil are obtained. Yield 90%
90%		c. (3-Bzomophenyl)methylamine; 5 ml of trifluoromethanesulfonic acid are added to a solution of 3.6 g (12.7 mmol) of tert-butyl (3-bromophenyl) -N-methylcarbamate in 15 mL of dichloromethane. The reaction medium is stirred for 1 hour at room temperature (RT) . The reaction is stopped by adding 50 ml of saturated sodium hydrogen carbonate solution and then extracted with ethyl acetate. The solvents are evaporated off and the residue is then chromatographed on silica gel, eluting with 1/1 heptane/ethyl acetate. 2.14 g of oil are obtained. 90% yield.
90%	With trifluoroacetic acid; In dichloromethane; at 20℃; for 1h;	3.6 g (12.7 mmol) of tert-butyl (3-bromophenyl)-N-methylcarbamate, prepared in a manner analogous to Example 1b), are dissolved in 15 ml of dichloromethane. 5 ml of trifluoroacetic acid are added and the reaction mixture is stirred at ambient temperature for 1 hour. The reaction is halted by the addition of 50 ml of a saturated sodium hydrogen- carbonate solution and then extraction is carried out with ethyl acetate. The organic phases are combined and dried over sodium sulphate. The solvents are evaporated and then the residue is chromatographed on silica gel (heptane/ethyl acetate 50/50). 2.14 g of 3-bromo-N-methylaniline are obtained in the form of an oil. Yield = 90%.

Reference： [1]Patent: US2009/12129,2009,A1 .Location in patent: Page/Page column 26
[2]Patent: US2010/286430,2010,A1 .Location in patent: Page/Page column 3
[3]Patent: US2009/12129,2009,A1 .Location in patent: Page/Page column 13-14
[4]Patent: WO2006/18326,2006,A1 .Location in patent: Page/Page column 17
[5]Patent: WO2006/53791,2006,A2 .Location in patent: Page/Page column 44
[6]Patent: WO2005/108352,2005,A1 .Location in patent: Page/Page column 34-35
[7]Angewandte Chemie - International Edition,2014,vol. 53,p. 7918 - 7922
Angew. Chem.,2014,vol. 53,p. 8052 - 8056,5

15
[ 4747-81-3 ]
[ 66584-32-5 ]
[ 877064-55-6 ]

Yield	Reaction Conditions	Operation in experiment
77 - 97%	With triethylamine; In tetrahydrofuran; at 20℃; for 12h;Product distribution / selectivity;	Example 25Synthesis of (Z)-3-[2-butoxy-3'-(3-heptyl-1-methylureido)biphenyl-4-yl]-2-methoxyacrylic acid a-1-(3-bromophenyl)-3-heptyl-1-methylureaIn a manner similar to that of Example 24g, by reacting 50 g (350 mmol) of heptyl isocyanate with 66 g (350 mmol) of (3-bromophenyl)methylamine (prepared as in Example 24f) in 300 mL of dichloromethane in the presence of 20 mL of triethylamine, 113 g (97%) of 1-(3-bromophenyl)-3-heptyl-1-methylurea are obtained.; Example 35Synthesis of (E)-3-[2-butoxy-3'-(3-heptyl-1-methylureido)biphenyl-4-yl]-2-methylacrylic acid a-1-(3-bromophenyl)-3-heptyl-1-methylurea3.2 mL (20 mmol) of heptyl isocyanate are added to a solution of 2.5 g (13 mmol) of (3-bromophenyl)methylamine (prepared according to Example 24f) in 10 mL of tetrahydrofuran in the presence of 2 mL of triethylamine. The reaction mixture is stirred for 12 hours at room temperature. The reaction is stopped by addition of 2 mL of water and extraction with ethyl acetate. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated off and the residue is then purified by chromatography on a column of silica eluted with a 70/30 heptane/ethyl acetate mixture. 3.4 g (77%) of 1-(3-bromophenyl)-3-heptyl-1-methylurea are obtained in the form of a solid.
77%	With triethylamine; In tetrahydrofuran; at 20℃; for 12h;	3.2 mL (20 mmol, 1.5 eq) of heptyl isocyanate are added to a solution of 2.5 g (13 mmol, 1 eq) of (3-bromophenyl)methylamine in 10 ml of tetrahydrofuran in the presence of 2 ml of triethylamine. The reaction mixture is stirred for 12 hours at r.t. The reaction is stopped by addition of 2 mL of water and then extracted with ethyl acetate. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated off and the residue is then chromatographed on silica gel (70/30 heptane/ethyl acetate). 3.4 g of 1-(3-bromophenyl)-3-heptyl-1-methylurea in solid form are obtained. Yield = 77 %
77%	With triethylamine; In tetrahydrofuran; at 20℃; for 12h;	3.2 ml (20 mmol) of heptyl isocyanate are added to a solution of 2.5 g (13 mmol) of (3-bromophenyl)methyl-amine, thus prepared, in 10 ml of tetrahydrofuran in the presence of 2 ml of triethylamine. The reaction mixture is stirred at ambient temperature for 12 hours. The reaction is halted by the addition of 2 ml of water and then extracted with ethyl acetate. The organic phases are combined and dried over sodium sulphate. The solvents are evaporated and then the residue is purified by chromatography on a column of silica eluted with a heptane/ethyl acetate 70/30 mixture. 3.4 g (77%) of 1-(3-bromophenyl)-3-heptyl-1-methylurea are obtained in the solid form.

Reference： [1]Patent: US2009/12129,2009,A1 .Location in patent: Page/Page column 27; 33
[2]Patent: WO2006/18326,2006,A1 .Location in patent: Page/Page column 17
[3]Patent: US2010/286430,2010,A1 .Location in patent: Page/Page column 3

16
[ 66584-32-5 ]
[ 877064-60-3 ]

Yield	Reaction Conditions	Operation in experiment
40%		e-3-Methylaminophenylboronic acid161 mL (242 mmol) of 1.5M methyllithium in diethyl ether are added dropwise to a solution precooled to -78 C. of 37.6 g (202 mmol) of (3-bromophenyl)methylamine (prepared according to Example 24f) in 300 mL of tetrahydrofuran. After stirring for 1 hour at -78 C., 261 mL (444 mmol) of a 1.7M solution of tert-butyllithium in pentane are added dropwise and the medium is again stirred at -78 C. for 1 hour. At -65 C., 103.5 mL (808 mmol) of trimethyl borate are added dropwise and the reaction medium is then stirred, while allowing the temperature to rise to room temperature over 1 hour. After addition of ice, the reaction medium is extracted with a 1/1 heptane/ethyl acetate mixture and then with 1-butanol. The organic phases are combined, washed with water, dried over magnesium sulfate, filtered and evaporated; 11 g (40%) of 3-methylaminophenylboronic acid are obtained.
11 - 40%		37.6 g (202 mmol, 1 eq) of (3-bromophenyl)methylamine (obtained as in 1c) are dissolved in 300 ml of tetrahydrofuran. The reaction mixture is cooled to -70C, and 166 mL (242 mmol, 1.2 eq) of 1.5 M methyllithium are then added slowly while maintaining the temperature at -70C. The reaction mixture is stirred for 1 hour at -70C. 306 mL (444 mmol, 2.2 eq) of 1.46 M tert-butyllithium are added while maintaining the temperature at -70C. The reaction mixture is stirred for 45 minutes at -70C. 103.5 mL (808 mmol, 4 eq) of trimethyl borate are added at -65C, and the reaction mixture is then warmed to room temperature. The reaction is stopped by addition of 1L of 1N hydrochloric acid. The pH is adjusted to 5 and the reaction medium is then extracted with n-butanol. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated off and the residue is then chromatographed on silica gel (70/30 heptane/ethyl acetate). 11.3 g of N-methyl-3-aminophenylboronic acid are obtained. Yield = 40 %

Reference： [1]Patent: US2009/12129,2009,A1 .Location in patent: Page/Page column 30
[2]Patent: WO2006/18326,2006,A1 .Location in patent: Page/Page column 22; 41

17
[ 3954-13-0 ]
[ 66584-32-5 ]
[ 877065-22-0 ]

Yield	Reaction Conditions	Operation in experiment
93%	With triethylamine; In dichloromethane; for 72h;Heating / reflux;	g-1-(3-bromophenyl)-1-methyl-3-pentylureaA solution of 50 g (0.45 mol) of pentyl isocyanate in 50 mL of dichloromethane is added to a mixture of 82 g (0.45 mol) of (3-bromophenyl)methylamine in 250 mL of dichloromethane in the presence of 20 mL (0.14 mol) of triethylamine. The reaction medium is heated at reflux for 3 days and then hydrolyzed in 200 mL of 1 N hydrochloric acid solution and extracted with ethyl acetate. The organic phases are combined, washed with water, with saturated sodium chloride solution and evaporated. 123 g (93%) of 1-(3-bromophenyl)-1-methyl-3-pentylurea are obtained.
93%	With triethylamine; In dichloromethane; for 72h;Heating / reflux;	A solution of 50.0 g (0.442 mol, 1 eq) of pentyl isocyanate in 50 mL of dichloromethane is added to a mixture of 82.2 g (0.442 mol, 1 eq) of (3-bromophenyl)methylamine in 250 mL of dichloromethane in the presence of 20 mL(0.143 mol, 0.3 eq) of triethylamine. The reaction medium is refluxed for 3 days and then hydrolysed in 200 mL of 1N hydrochloric acid solution and extracted with ethyl acetate. The organic phases are combined, washed with water and sodium chloride, and evaporated. 123 g of 1-(3-bromophenyl)-1-methyl-3-pentylurea are obtained. Yield = 93%

Reference： [1]Patent: US2009/12129,2009,A1 .Location in patent: Page/Page column 26
[2]Patent: WO2006/18326,2006,A1 .Location in patent: Page/Page column 75; 76

18
[ 873-32-5 ]
[ 66584-32-5 ]
[ 1021397-50-1 ]

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 1932 - 1934

19
[ 66584-32-5 ]
[ 87199-17-5 ]
[ 398151-09-2 ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃; for 2h;	b-3'-Methylaminobiphenyl-4-carbaldehyde5 g (26.8 mmol) of 3-bromophenylmethylamine and 4 g (26.8 mmol) of commercial 4-formylbenzeneboronic acid are dissolved in 50 mL of an aqueous 6/1 mixture of dimethylformamide/aqueous 2 M potassium phosphate. 1.5 g (1.3 mmol, 5 mol %) of tetrakis(triphenylphosphine)palladium are added. The mixture is stirred for 2 hours at 90 C. The reaction is worked up by addition of 50 mL of water and extraction with ethyl acetate. The organic phases are washed with sodium chloride solution and dried over magnesium sulfate. The solvents are evaporated off, and the residue is then purified by chromatography on a column of silica eluted with a 7/3 heptane/ethyl acetate mixture. 4.3 g (76%) of 3'-methylaminobiphenyl-4-carbaldehyde are obtained.

Reference： [1]Patent: US2009/12129,2009,A1 .Location in patent: Page/Page column 14

20
[ 935397-19-6 ]
[ 66584-32-5 ]
[ 935397-46-9 ]

Yield	Reaction Conditions	Operation in experiment
87%	With cesium fluoride;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In diethylene glycol dimethyl ether; at 80℃; for 18.3333h;Product distribution / selectivity;	b-Ethyl (Z)-2-ethoxy-3-(3'-methylaminobiphenyl-4-yl)acrylate1.0 g (2.9 mmol) of ethyl (Z)-2-ethoxy-3-[4-(4,4,5,5-tetramethyl[1.3]dioxaborolan-2-yl)phenyl]acrylate, 0.45 g (2.4 mmol) of (3-bromophenyl)methylamine (prepared according to Example 24f) and 1.1 g (7.2 mmol) of caesium fluoride are dissolved in 60 mL of diethylene glycol dimethyl ether. After bubbling nitrogen through the reaction mixture for 20 minutes, 0.12 g (0.15 mmol) of dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium is added. The reaction mixture is heated at 80 C. for 18 hours with vigorous stirring. After cooling, the reaction is worked up by addition of 60 mL of water and extraction with ethyl acetate. The organic phases are combined, washed with saturated aqueous sodium chloride solution and then dried over magnesium sulfate. After filtration, the solvents are evaporated off. The crude product obtained is purified by chromatography on a column of silica eluted with a 90/10 heptane/ethyl acetate mixture to give 0.68 g (87%) of ethyl (Z)-2-ethoxy-3-(3'-methylaminobiphenyl-4-yl)acrylate.

Reference： [1]Patent: US2009/12129,2009,A1 .Location in patent: Page/Page column 38

21
[ 13061-96-6 ]
[ 591-19-5 ]
[ 66584-32-5 ]

Reference： [1]Organic Letters,2009,vol. 11,p. 1677 - 1680

22
[ 66584-32-5 ]
[ 124-63-0 ]
[ 875917-18-3 ]

Yield	Reaction Conditions	Operation in experiment
53%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃;	a) λ/-(3-Bromophenyl)-λ/-methylmethanesulfonamide3-Bromo-N-methylaniline (0.24 mL, 1.9 mmol) and DIPEA (0.36 mL, 2.1 mmol) were mixed in dry DCM (5 mL) and cooled to 0 0C. Methanesulphonylchloride (0.15 mL, 1.9 <n="55"/>mmol) was added dropwise at 0 0C. The reaction mixture was allowed to reach RT and stirred overnight. The reaction was quenched with water and extracted with DCM. The combined organic layers were washed with 0.1N HCl, dried (Na2SO4) and concentrated. The residue was purified by column chromatography eluting with heptane/EtOAc 3:1 to give a solid product (0.27 g, 53%).1H-NMR (300 MHz, DMSOd6): δ 7.63 (t, J= 2.0 Hz, IH), 7.53 - 7.49 (m, IH), 7.46 - 7.34 (m, 2H), 3.24 (s, 3H), 2.98 (s, 3H); GC-MS m/z: 263/265 1:1 [M+].

Reference： [1]Patent: WO2009/7747,2009,A2 .Location in patent: Page/Page column 53-54

23
[ 66584-32-5 ]
[ 109-94-4 ]
[ 502925-17-9 ]

Yield	Reaction Conditions	Operation in experiment
60%	at 80℃; for 60h;	3 -BromophenvKmethvDformamide 3-Bromo-7V-methylaniline (1 g, 5.4 mmol) in ethylformate (2 mL) was heated to 80 0C for 60 h. The reaction mixture was concentrated and purified by column chromatography eluting with a heptane to heptane/ethyl acetate 4:1 to give the subtitle compound (0.7 g, 60%).1H-NMR (DMSOd6): δ 8.58 and 8.37 rotamers 7:1 (s, IH), 7.83 - 7.80 and 7.63 - 7.61 rotamers 1:7 (m, IH), 7.47 - 7.35 (m, 3H), 3.20 (s, 3H); APCI-MS m/z: 214/216 1:1 [MH+].

Reference： [1]Patent: WO2009/7747,2009,A2 .Location in patent: Page/Page column 40

24
[ 7253-22-7 ]
[ 66584-32-5 ]
[ 1202228-17-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 6623 - 6626

25
[ 38267-96-8 ]
[ 66584-32-5 ]
[ 1202228-33-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 6623 - 6626

26
[ 121-43-7 ]
[ 66584-32-5 ]
[ 877064-60-3 ]

Yield	Reaction Conditions	Operation in experiment
40%		d. N-Methyl -3-ami.τιophenylboron+/-c add; 37 . 6 g ( 202 mmol, 1 eq) of EPO <DP n="46"/>(3-bromoρhenyl)methylamine (obtained as in Ic) are dissolved in 300 mL of tetrahydrofuran. The reaction mixture is cooled to -700C and 166 mL (242 mmol, 1.2 eq) of 1.5 M methyllithium are then added slowly, while keeping the temperature at -700C. The reaction mixture is stirred for 1 hour at -700C. 306 mL (444 mmol, 2.2 eq) of 1.46 M tert-butyllithium are added, while keeping the temperature at -700C. The reaction mixture is stirred for 45 minutes at -700C. 103.5 ml (808 mmol, 4 eq) of trimethyl borate are added at -650C and the reaction mixture is then warmed to room temperature. The reaction is stopped by adding 1 L of IN hydrochloric acid. The pH is adjusted to pH 5 and the reaction medium is then extracted with n-butanol. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated off and the residue is then chromatographed on silica gel (70/30 heptane/ethyl acetate) . 11.3 g of N-methyl-3- aminophenylboronic acid are obtained. Yield = 40%.

Reference： [1]Patent: WO2006/53791,2006,A2 .Location in patent: Page/Page column 44-45

27
[ 66584-32-5 ]
[ 1711-05-3 ]
[ 1268826-63-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With triethylamine; In dichloromethane; at 0 - 20℃;	N-Methylaniline derivative (1 equiv) was mixed with Et3N (2 equiv) in dichloromethane. The solution was cooled at 0 C. The acyl chloride (1.2 equiv) was slowly added and the mixture stirred at room temperature for 1 h. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and concentrated to dryness under reduced pressure. The product was purified by column chromatography.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 807 - 815

28
[ 66584-32-5 ]
[ 98-88-4 ]
[ 51774-35-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With triethylamine; In dichloromethane; at 0 - 20℃;	N-Methylaniline derivative (1 equiv) was mixed with Et3N (2 equiv) in dichloromethane. The solution was cooled at 0 C. The acyl chloride (1.2 equiv) was slowly added and the mixture stirred at room temperature for 1 h. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and concentrated to dryness under reduced pressure. The product was purified by column chromatography.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 807 - 815
[2]Organic Letters,2020,vol. 22,p. 4583 - 4587

29
[ 66584-32-5 ]
[ 100-07-2 ]
N-(3-bromophenyl)-4-methoxy-N-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine; In dichloromethane; at 0 - 20℃;	N-Methylaniline derivative (1 equiv) was mixed with Et3N (2 equiv) in dichloromethane. The solution was cooled at 0 C. The acyl chloride (1.2 equiv) was slowly added and the mixture stirred at room temperature for 1 h. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and concentrated to dryness under reduced pressure. The product was purified by column chromatography.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 807 - 815

30
[ 66584-32-5 ]
[ 4693-91-8 ]
[ 1268826-67-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine; In dichloromethane; at 0 - 20℃;	N-Methylaniline derivative (1 equiv) was mixed with Et3N (2 equiv) in dichloromethane. The solution was cooled at 0 C. The acyl chloride (1.2 equiv) was slowly added and the mixture stirred at room temperature for 1 h. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and concentrated to dryness under reduced pressure. The product was purified by column chromatography.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 807 - 815

31
[ 66584-32-5 ]
[ 6834-42-0 ]
[ 1268826-65-8 ]

Yield	Reaction Conditions	Operation in experiment
98%	With triethylamine; In dichloromethane; at 0 - 20℃;	N-Methylaniline derivative (1 equiv) was mixed with Et3N (2 equiv) in dichloromethane. The solution was cooled at 0 C. The acyl chloride (1.2 equiv) was slowly added and the mixture stirred at room temperature for 1 h. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and concentrated to dryness under reduced pressure. The product was purified by column chromatography.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 807 - 815

32
[ 253878-91-0 ]
[ 66584-32-5 ]

Reference： [1]Chinese Chemical Letters,2010,vol. 21,p. 939 - 942

33
[ 591-19-5 ]
[ 66584-32-5 ]

Reference： [1]Chinese Chemical Letters,2010,vol. 21,p. 939 - 942
[2]Angewandte Chemie - International Edition,2014,vol. 53,p. 7918 - 7922
Angew. Chem.,2014,vol. 53,p. 8052 - 8056,5
[3]Patent: WO2005/108352,2005,A1
[4]Patent: US2020/87326,2020,A1

34
[ 638-07-3 ]
[ 66584-32-5 ]
[ 1364822-77-4 ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 3462 - 3467
[2]Journal of Medicinal Chemistry,2013,vol. 56,p. 2665 - 2675

35
[ 66584-32-5 ]
[ 103-80-0 ]
[ 1382354-44-0 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 5760 - 5773
[2]Chemical Communications,2022,vol. 58,p. 1382 - 1385

36
[ 66584-32-5 ]
[ 98-80-6 ]
N-methyl-[1,1'-biphenyl]-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 6h;Inert atmosphere;	3-Bromo-N-methylaniline (93 mg, 0.5 mmol), phenyl boronic acid (78 mg, 0.6 mmol), sodium carbonate (2 ml, 2N aqueous) and tetrakis(triphenylphosphine) palladium (58 mg, 0.05 mmol) in a DME (2 ml) solution was stirred at 80 C for 6 hours under nitrogen. The reaction mixture was cooled to rt. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulphate, filtered and concentrated to dryness. The product was purified by FC with hexane/ethyl acetate (15 : 1) as eluent, yielded as colorless oil (60 mg, 66%); MS (ESI) : 184 (M + H)+; ^ N M R (CD3COCD3) : 2.84 (s, 3H), 5.02 (br s, 1 H), 6.60 (ddd, J= 8.1, 2.1, 0.9 Hz, 1H), 6.85-6.87 (m, 2H), 7.19 (t, J= 8.1 Hz, 1H), 7.30-7.33 (m, 1 H), 7.42 (t, J= 7.6 Hz, 2H), 7.59-7.61 (m, 2H); 13C N M R (CD3COCD3) : 30.5, 111.2, 112.0, 115.8, 127.7, 127.8, 129.5, 130.2, 142.7, 142.9, 151.5.

Reference： [1]Patent: WO2012/117097,2012,A1 .Location in patent: Page/Page column 63

37
[ 66584-32-5 ]
1-(benzyloxy)but-3-en-2-yl 2,2,2-trichloroacetimidate [ No CAS ]
[ 1404461-88-6 ]
C₁₈H₂₀BrNO [ No CAS ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 11531 - 11533,3

38
[ 66584-32-5 ]
[ 17405-06-0 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 5294 - 5297
[2]Journal of the American Chemical Society,2013,vol. 135,p. 468 - 473
[3]Chemistry - A European Journal,2014,vol. 20,p. 14245 - 14249
[4]Chemistry - An Asian Journal,2017,vol. 12,p. 2804 - 2808
[5]Organic and Biomolecular Chemistry,2018,vol. 16,p. 4471 - 4481
[6]Chemical Communications,2018,vol. 54,p. 7794 - 7797
[7]Organic and Biomolecular Chemistry,2020,vol. 18,p. 4014 - 4018
[8]Chemical Communications,2020,vol. 56,p. 7415 - 7418

39
[ 66584-32-5 ]
[ 826-72-2 ]

Reference： [1]Journal of the American Chemical Society,2013,vol. 135,p. 468 - 473
[2]Journal of the American Chemical Society,2013,vol. 135,p. 468 - 473

40
[ 66584-32-5 ]
[ 2905-24-0 ]
[ 1492050-29-9 ]

Yield	Reaction Conditions	Operation in experiment
82%	With tetra(n-butyl)ammonium hydrogensulfate; sodium hydroxide; In dichloromethane; water; at 20℃; for 3h;	General procedure: To a solution of substituted N-methylaniline (1mmol) in CH2Cl2 (5mL) was added aqueous NaOH 25M (1mL) followed by tetrabutylammonium hydrogen sulfate (0.15mmol). After 5min of vigorous stirring, the substituted benzenesulfonyl chloride (1mmol) was added to the reaction mixture. The solution was stirred either for 3h or overnight at room temperature. Water was added to quench the reaction. Aqueous layer was extracted with CH2Cl2 (3×CH2Cl2). The organic layer was washed once with brine and once with water, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using a mixture of n-hexane and ethyl acetate as solvent to afford the desired compound.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 69,p. 201 - 215

41
[ 66584-32-5 ]
[ 1214350-99-8 ]
[ 1492050-30-2 ]

Yield	Reaction Conditions	Operation in experiment
67%	With tetra(n-butyl)ammonium hydrogensulfate; sodium hydroxide; In dichloromethane; water; at 20℃; for 3h;	General procedure: To a solution of substituted N-methylaniline (1mmol) in CH2Cl2 (5mL) was added aqueous NaOH 25M (1mL) followed by tetrabutylammonium hydrogen sulfate (0.15mmol). After 5min of vigorous stirring, the substituted benzenesulfonyl chloride (1mmol) was added to the reaction mixture. The solution was stirred either for 3h or overnight at room temperature. Water was added to quench the reaction. Aqueous layer was extracted with CH2Cl2 (3×CH2Cl2). The organic layer was washed once with brine and once with water, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using a mixture of n-hexane and ethyl acetate as solvent to afford the desired compound.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 69,p. 201 - 215

42
[ 66584-32-5 ]
[ 15486-96-1 ]
[ 1610998-44-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In water; ethyl acetate; at 20℃; for 0.333333h;Cooling with ice;	The suitable ω-bromoalkanoyl chloride (0.7 mmol) was added dropwise to a stirred ice-cooled solution of the suitable aniline (0.33 mmol) and NaHCO3 (0.10 g, 1.22 mmol) in EtOAc (0.4 mL) and water (0.4 mL), and the resulting mixture was stirred at room temperature for 20 min. Water was added and the aqueous phase was extracted three times with EtOAc. The combined organic phases were washed with brine, dried (Na2SO4) and concentrated under reduced pressure to afford a crude residue that was used for the next step, without further purification.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 80,p. 8 - 35

43
[ 66584-32-5 ]
[ 503-60-6 ]
[ 1608130-86-4 ]

Reference： [1]Organometallics,2014,vol. 33,p. 2628 - 2640

44
[ 100-42-5 ]
[ 66584-32-5 ]
3-bromo-N-(3-phenylpropyl)aniline [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2014,vol. 53,p. 7918 - 7922
Angew. Chem.,2014,vol. 53,p. 8052 - 8056,5

45
[ 25216-74-4 ]
[ 66584-32-5 ]

Reference： [1]Angewandte Chemie - International Edition,2014,vol. 53,p. 7918 - 7922
Angew. Chem.,2014,vol. 53,p. 8052 - 8056,5
[2]Patent: WO2005/108352,2005,A1

46
[ 5256-74-6 ]
[ 66584-32-5 ]
diethyl 2-[N-(3-bromophenyl)-N-methylamino]propanedioate [ No CAS ]

Reference： [1]Australian Journal of Chemistry,2014,vol. 67,p. 1211 - 1216

47
[ 66584-32-5 ]
[ 1226985-36-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: hydrogenchloride; sodium nitrite / water / 10 °C / Cooling with ice 2.1: sodium acetate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; silver hexafluoroantimonate / 1,2-dichloro-ethane / 0.17 h / Inert atmosphere; Glovebox; Sealed tube 2.2: 24 h / 50 °C / Inert atmosphere; Sealed tube 3.1: potassium <i>tert</i>-butylate / dichloromethane / 18 h / Schlenk technique 3.2: Schlenk technique

Reference： [1]Chen, Jinsen; Chen, Pei; Song, Chao; Zhu, Jin [Chemistry - A European Journal, 2014, vol. 20, # 44, p. 14245 - 14249]

48
[ 66584-32-5 ]
[ 41279-57-6 ]
1-(3-bromophenyl)-1-methyl-3-(naphthalen-1-yl)guanidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%		General procedure: S7 (0.35 g, 2 mmol) was dissolved in Et2O (5 mL) and converted into its hydrochloride salt by drop-wise addition of aq. HCl (1 M) in Et2O. The resulting precipitate was collected byfiltration, dried for 10 min, and used in the subsequent reaction. A mixture of S7 hydrochloride (212 mg, 1 mmol), S1 (185 mg, 1.1 mmol), and toluene (2 mL) was heated to 130 oC,stirred for 21 h, cooled to rt, and diluted with MeOH (5 mL). This solution was concentrated onto silicagel and purified on a silica gel column with gradient elution (EtOAc EtOAc-MeOH;4: 1 v/v). The fractions containing the desired guanidine were collected, concentrated under reduced pressure, andapplied to a second silica gel column eluted with Et3N-EtOAc-hexanes(5: 20: 75 by vol.) to afford 20 asa white solid

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 225 - 228

49
[ 67-56-1 ]
[ 7677-24-9 ]
[ 66584-32-5 ]
2-((3-bromophenyl)(methyl)amino)acetonitrile [ No CAS ]

Reference： [1]Chemical Communications,2016,vol. 52,p. 2776 - 2779

50
[ 67-56-1 ]
[ 591-19-5 ]
[ 66584-32-5 ]

Yield	Reaction Conditions	Operation in experiment
93%	With [(η5-pentamethylcyclopentadienyl)IrIIIbis-(κC-1,3-dimethylimidazol-2-ylidene)Cl]BF4; potassium hydroxide; In toluene; at 100℃; for 12h;Sealed tube;	General procedure: To a 15 mL sealing tube, was added the amine (0.5 mmol),MeOH (100 lL), Ir3 (0.5 mol%) and KOH (75 mol%), and the tubewas closed with a screw-top cap. Next, the reaction mixture wasstirred for 12 h at 100 C. After cooling to room temperature, themixture was diluted with ethyl acetate and filtered through a shortpad of silica (2 cm in a Pasteur pipette). The silica was washed withethyl acetate. The filtrate was evaporated and the crude residuewas purified by column chromatography (SiO2, petroleum ether:ethyl acetate = 80:1).

Reference： [1]Organic Letters,2018,vol. 20,p. 5985 - 5990
[2]Organometallics,2020,vol. 39,p. 3514 - 3523
[3]Dalton Transactions,2019,vol. 48,p. 5072 - 5082
[4]Advanced synthesis and catalysis,2017,vol. 359,p. 4278 - 4283
[5]Polyhedron,2021,vol. 205
[6]Journal of Catalysis,2017,vol. 347,p. 57 - 62
[7]Catalysis science and technology,2022,vol. 12,p. 67 - 74
[8]Organic and Biomolecular Chemistry,2021,vol. 19,p. 3451 - 3461
[9]Organometallics,2018,vol. 37,p. 3353 - 3359
[10]Chemical Communications,2016,vol. 52,p. 2776 - 2779

51
[ 55552-70-0 ]
[ 66584-32-5 ]
C₁₁H₁₁NO [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 2810 - 2814
Angew. Chem.,2016,vol. 128,p. 2860 - 2864,5

52
[ 674-82-8 ]
[ 66584-32-5 ]
C₁₁H₁₂BrNO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In toluene; at 100℃; for 6h;	A mixture of <strong>[66584-32-5]N-methyl-3-bromoaniline</strong> (K-2) (2.45 g, 13.1 mmol), diketene (1.22 g, 14.5 mmol), and toluene (10mL) was heated to 100C, and stirred for 6 hours. The solvent was evaporated under reduced pressure, the resultingcompound represented by the structural formula (K-3) was added to polyphosphoric acid (10 mL) heated to 100C, andthe resulting mixture was stirred for 5 hours with heating. The reaction mixture was cooled to room temperature, water(100 mL) was added to the mixture, and the deposited solid was collected by filtration, and washed with hexane to givethe compound represented by the structural formula (K-4) (631 mg, 2.50 mmol, yield 19%).1H-NMR Spectrum (300MHz, CDCl3):δ (ppm): 2.44 (3H, s), 3.67 (3H, s), 6.60 (1H, s), 7.37 (1H, dd, J=8.1Hz, 1.8Hz), 7.53-7.56 (2H, m)

Reference： [1]Patent: EP2987787,2016,A1 .Location in patent: Paragraph 0122

53
[ 50-00-0 ]
[ 591-19-5 ]
[ 66584-32-5 ]
[ 100-61-8 ]

Yield	Reaction Conditions	Operation in experiment
11%Spectr.; 10%Spectr.	With calcium hydride; 5%-palladium/activated carbon; In toluene; at 30℃; for 16h;Sealed tube;	General procedure: In a sealed tube was introduced an amine (1 equiv), paraformaldehyde (1 equiv) in toluene (0.5 M) followed by the addition at room temperature under of argon of palladium on carbon 5% (2 mol %) and then calcium hydride (60 mol %). The pressure tube was closed and introduced in a preheated oil bath at 30C where it was stirred for 16 h at 700 rpm.

Reference： [1]Tetrahedron Letters,2016,vol. 57,p. 3002 - 3005

54
[ 66584-32-5 ]
[ 32857-62-8 ]
N-(3-bromophenyl)-N-methyl-2-(4-(trifluoromethyl)phenyl)acetamide [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 4954 - 4957

55
[ 66584-32-5 ]
[ 75927-49-0 ]
(E)-N-methyl-3-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)aniline [ No CAS ]

Reference： [1]New Journal of Chemistry,2017,vol. 41,p. 3172 - 3176

56
[ 66584-32-5 ]
[ 18001-18-8 ]
N-(2-methyl-3-(dimethyl(phenyl)silyl)propyl)-3-bromoaniline [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 4197 - 4202

57
[ 66584-32-5 ]
[ 18752-21-1 ]
N-(2-methyl-3-(triphenylsilyl)propyl)-3-bromoaniline [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 4197 - 4202

58
[ 66584-32-5 ]
[ 762-72-1 ]
N-(2-methyl-3-(trimethylsilyl)propyl)-3-bromoaniline [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 4197 - 4202

59
[ 542-05-2 ]
[ 66584-32-5 ]
N1,N5-bis(3-bromophenyl)-N1,N5-dimethyl-3-oxopentanediamide [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2017,vol. 359,p. 2542 - 2548

60
[ 50-00-0 ]
[ 591-19-5 ]
[ 66584-32-5 ]

Reference： [1]Organic and Biomolecular Chemistry,2018,vol. 16,p. 4701 - 4714
[2]Advanced Synthesis and Catalysis,2017,vol. 359,p. 2542 - 2548

61
[ 616-38-6 ]
[ 591-19-5 ]
[ 66584-32-5 ]

Yield	Reaction Conditions	Operation in experiment
96%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In 1-methyl-pyrrolidin-2-one; at 250℃; for 0.2h;Flow reactor;	General procedure: Selective N-monomethlyation reactions were performed in a Vapourtec E-series continuous flow system equipped with a high temperature tube reactor (10 mL, stainless steel, 0.03'' i.d., Fig. 2 ) and a membrane back pressure regulator (Zaiput). Stock solutions of aniline (20 mmol, 1.0 equiv, 2 M), DMC (5.05 mL, 60 mmol, 3.0 equiv, 6 M), and DBU (4.47 mL, 30 mmol, 1.5 equiv, 3 M) were prepared in oven-dried 10 mL volumetric flasks using NMP as the solvent. The solutions were transferred to screw-thread vials with septum caps and reagents were pumped directly from the vials. After the high temperature coiled tube reactor was heated to 250 C, peristaltic pumps (Vapourtec V-3) were used to pump the reactant solutions into the system (0.277 mL/min each for a 12 min residence time). The solutions were mixed with a cross-mixer (0.4″ i.d.), passed though the high temperature coiled tube reactor. Upon exiting the reactor, the reaction stream was passed through a short segment of stainless steel tubing to enable the reaction to cool and then exited the system by passage through the back pressure regulator (Note: PFA fittings should not be used at the exit of the reactor as they will deform due to the high temperature of the reaction stream and cause leaks in the system. Stainless steel connectors and tubing (12'') were used in our system.). After the flow system was equilibrated for 18 min, the product stream was collected for 5 min (2.77 mmol of aniline). The crude mixture was dissolved in ethyl acetate and washed with brine. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (Biotage 25 g Ultra-sil, 3-15% ethyl acetate in hexanes) to afford the desired product.

Reference： [1]Tetrahedron,2018,vol. 74,p. 3124 - 3128

62
[ 66584-32-5 ]
[ 109-77-3 ]
3-bromo-N-methyl-4-selenocyanatoaniline [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2018,vol. 16,p. 4701 - 4714

63
[ 66584-32-5 ]
(2S,5S)-5-benzyl-2-(tert-butyl)-3-methyl-4-oxoimidazolidine-1-carbonyl chloride [ No CAS ]
C₂₃H₂₈BrN₃O₂ [ No CAS ]

Reference： [1]Nature,2018,vol. 562,p. 105 - 109

64
[ 66584-32-5 ]
[ 84827-47-4 ]
C₂₀H₂₅BrN₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With methylene blue; In acetonitrile; at 50℃; for 24h;Irradiation;	General procedure: A suspension of N-arylglycine ester 1 (0.5 mmol), N-substituted anilines 2 (0.6 mmol) and Methylene blue (0.025 mmol) in CH3CN was stirred for 24 h at 50 C under an air atmosphere irradiated by blue lights. After cooling, water (10 mL) was added and the mixture was extracted with CH2Cl2 (3 x 10 mL). The combined organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residues were purified by flash column chromatography (n-hexane-EtOAc) to afford the desired product 3.
42%	With Acr+-Mes ClO4-; In acetonitrile; at 30℃; for 24h;Irradiation; Green chemistry;	tert-Butyl 2-(p-toluidine)acetate (0.5 mmol, 110.6 mg),<strong>[66584-32-5]N-methyl m-bromoaniline</strong> (1.5 mmol, 277.5 mg),Acr+-Mes ClO4-(0.01 mmol, 4.1 mg) was added to a 25 mL two-necked flask.Add acetonitrile (5 mL) as solvent.Stir,Under the blue light emitted by a 3W LED lamp,Reacted in an air atmosphere at 30 C for 24 h,After the reaction,Water and dichloromethane are added to the reaction system.Extraction layering,Divided into water and organic layers,Drying with anhydrous sodium sulfate in the organic layer,The dried organic layer was concentrated by distillation under reduced pressure to give a yellow oil.Yellow colorThe oil is separated and purified by column chromatography on silica gel.a mixture of petroleum ether and ethyl acetate in a volume ratio of 30:1 as a washDissolve, collect the eluent and evaporate the solvent.84.9 mg of a white solid product was obtained.The yield is 42%, that is, the target product is obtained, and its structural formula is:

Reference： [1]Tetrahedron Letters,2018,vol. 59,p. 4364 - 4369
[2]Patent: CN109265360,2019,A .Location in patent: Paragraph 0025

65
[ 667-27-6 ]
[ 66584-32-5 ]
[ 502925-17-9 ]

Yield	Reaction Conditions	Operation in experiment
74%	With water; In N,N-dimethyl-formamide; at 110℃; for 6h;Schlenk technique;	General procedure: A 25 mL oven-dried Schlenk tube was sequentially added N-methylaniline 1 or aniline 4 (0.2 mmol), Ethyl Bromodifluoroacetate 2a (81.2 mg, 0.4 mmol), DMF (1ml) and H2O (1 mL) was added under air. The reaction mixture was stirred for 6 h at 110. The solution was then diluted with ethyl acetate (20 mL), washed with brine (10 mL), extracted with ethyl acetate (3*5 mL), dried over anhydrous Na2SO4, filtered and evaporated under vacuum. The crude reaction mixture was purified by column chromatography (silica gel, ethyl acetate/petroleum ether) yielded the desired product 3 or 5.
69%	With copper (I) acetate; caesium carbonate; XPhos; In N,N-dimethyl-formamide; at 110℃; for 12h;	37 mg (0.2 mmol) of <strong>[66584-32-5]N-methyl-3-bromoaniline</strong>, 81.2 mg of ethyl bromodifluoroacetate (0.4 mmol), 2.5 mg (0.02 mmol) of cuprous acetate, 19.1 mg (0.04 mmol) of X-phos, 32.7 mg (0.2 mmol) of cesium carbonate were added to 2 mL of DMF solvent. The reaction was carried out at 110 C for 12 hours, after the reaction was completed, it was cooled, filtered, and the filtrate was evaporated. The solvent was removed and the residue was chromatographed on silica gel. It was washed with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 8:1. The effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the product was combined. The solvent was distilled off by a rotary evaporator. Drying in vacuo to give the yellow liquid N-methyl-N-(3-bromophenyl)carboxamide 29.4 mg, yield 69%.

Reference： [1]Tetrahedron Letters,2019,vol. 60,p. 1254 - 1258
[2]Patent: CN108774147,2018,A .Location in patent: Paragraph 0034
[3]Journal of Organic Chemistry,2018,vol. 83,p. 12815 - 12821

66
[ 66584-32-5 ]
[ 88284-48-4 ]
2-((3-bromophenyl)(methyl)amino)benzenesulfonyl fluoride [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 428 - 433

67
[ 6737-11-7 ]
[ 66584-32-5 ]
(S)-3-bromo-N-(but-3-en-2-yl)-N-methylaniline [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 671 - 676

68
[ 66584-32-5 ]
cyclobutanone O-benzoyl oxime [ No CAS ]
C₁₁H₁₃BrN₂ [ No CAS ]

Reference： [1]Chemical Communications,2019,vol. 55,p. 5347 - 5350

69
[ 35349-68-9 ]
[ 32315-10-9 ]
[ 66584-32-5 ]
C₃₂H₃₀BrNO₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%		Weigh BTC (58mg, 0.2mmol) in a 25mL two-neck bottle.Add 5 mL of anhydrous dichloromethane and stir with magnetic force.Equivalent to 25mL constant pressure dropping funnel<strong>[66584-32-5]N-methyl m-bromoaniline</strong>,Triethylamine (0.25 mmol) and 5 mL of dichloromethane, under ice bath,Slowly add dropwise, remove the ice salt bath after the end of the addition, and stir at room temperature for 4 h.HZA (40 mg, 0.1 mmol) was added to a 10 ml vial, and traces of DMAP, 5 mL of dichloromethane were added, and magnetically stirred at room temperature until completely dissolved.The solution was slowly added dropwise to the above reaction solution under ice salt bath, and the ice salt bath was removed by dropwise addition, and stirred at room temperature. After the reaction is completed, 3 to 6 times the volume of the reaction liquid is added to the above reaction liquid, and extracted with ethyl acetate for 3-5 times, and the organic layer is combined.Wash with saturated NaCl solution and dry with anhydrous Na2SO4.The mixture was suction filtered and concentrated to give a crude oil, which was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 20:1.Collecting an eluent that is strongly UV at 254 nm and less polar than HZA,The combined eluate and the product obtained by evaporating the solvent under reduced pressure are dried to obtain HZAM-16.The yield was 91%.

Reference： [1]Patent: CN109956952,2019,A .Location in patent: Paragraph 0128-0133

70
[ 66584-32-5 ]
[ 762-21-0 ]
diethyl 4-bromo-1-methyl-1H-indole-2,3-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With 1-iodo-2,2,3,3,4,4,5,5,5-nonafluorobutane; triethylamine; In acetonitrile; for 12h;Irradiation;	0.1 mmol of <strong>[66584-32-5]3-bromo-N-methylaniline</strong> was added to the reaction tube. 0.15 mmol of diethyl acetylene dicarboxylate, 0.15mmol perfluoroiodobutane, 0.1 mmol of triethylamine, 1mL acetonitrile, Under the illumination of 425nm light source, Stir the reaction for 12 hours, After the reaction is completed, it is separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluate is 5:1. The purified target product was obtained in a yield of 55%. The purity is 99.9%.

Reference： [1]Patent: CN110078655,2019,A .Location in patent: Paragraph 0116-0123

71
[ 66584-32-5 ]
[ 762-21-0 ]
diethyl 4-bromo-1-methyl-1H-indole-2,3-dicarboxylate [ No CAS ]
diethyl 6-bromo-1-methyl-1H-indole-2,3-dicarboxylate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2019,vol. 84,p. 14168 - 14178

72
[ 66584-32-5 ]
[ 637-44-5 ]
N-methyl-N-(3-bromophenyl)-3-phenylpropargylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 20℃;	General procedure: Dichloromethane (20 mL) and phenylpropynoic acid (11 mmol) were added into a 50 mL round bottom glass flask, and then N-alkylaniline (10 mol) was added at 0 C. Thereafter, a solution of DCC (15 mol), DMAP (0.5 mmol) and dichloromethane (20 mL) was slowly added dropwise with stirring. The reaction mixture was allowed to warm to room temperature and then stirred overnight. The mixture was washed with 5 mL saturated NaCO3 solution, 5 mL saturated NaCl solution, and 5 mL water. The organic phase was dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate as the eluent) affording the corresponding N-phenylpropynamide 1.

Reference： [1]Tetrahedron,2019,vol. 75

73
[ 74-85-1 ]
[ 66584-32-5 ]
[ 877065-06-0 ]
3-bromo-N-(pentan-3-yl)aniline [ No CAS ]

Reference： [1]Chemistry - A European Journal,2020,vol. 26,p. 2138 - 2142

74
[ 66584-32-5 ]
4-(6,9-dioxo-5-[[4-(trifluoromethyl)phenyl]methyl]-2,5,8-triazaspiro[3.5]nonan-8-yl)-3-fluorobenzonitrile [ No CAS ]
3-fluoro-4-[2-[3-(methylamino)phenyl]-6,9-dioxo-5-[[4-(trifluoromethyl)phenyl]methyl]-2,5,8-triazaspiro[3.5]nonan-8-yl]benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43 mg	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos; In 1,4-dioxane; at 80℃; for 3h;Inert atmosphere;	To a solution of 4-(6,9-dioxo-5-[[4-(trifluoromethyl)phenyl]methyl]-2,5,8- triazaspiro[3.5]nonan-8-yl)-3-fluorobenzonitrile (100.0 mg, 0.23 mmol, 1.0 equiv) in dioxane (2.0 mL) were added 3-bromo-/V-methylaniline (50.0 mg, 0.27 mmol, 1.2 equiv), Pd2(dba)3 (24.0 mg, 0.03 mmol, 0.11 equiv), X-phos (22.0 mg, 0.05 mmol, 0.2 equiv) and Cs2C03 (151.0 mg, 0.5 mmol, 2.0 equiv). The resulting mixture was stirred at 80 C for 3h under nitrogen atmosphere, cooled to rt, and purified by Prep-TLC (PE/EtOAc 1/1) to afford a mixture, which was purified by Prep-HPLC with the following conditions (SHIMADZU (HPLC-01)): Column, Xselect CSH OBD Column 30* l50mm 5um; mobile phase, Water (lOmM, NH4HC03) and ACN (45% gradient up to 80% in 9 min); Detector, UV254/220nm) to afford 43mg of 3-fluoro-4-[2-[3-(methylamino)phenyl]-6,9-dioxo-5-[[4- (trifluoromethyl)phenyl]methyl]-2,5,8-triazaspiro[3.5]nonan-8-yl]benzonitrile (Compound 536) as an off-white solid. LRMS (ES) m/z 538 (M+H). NMR (300 MHz, Chloroform-d) d 7.69 - 7.38 (m, 7H), 7.07 (t, J = 7.9 Hz, 1H), 6.17 (d, J = 8.0 Hz, 1H), 5.87 (d, J = 7.9 Hz, 1H), 5.70 (s, 1H), 5.28 (s, 2H), 4.53 (d, J = 8.3 Hz, 2H), 4.45 (s, 2H), 4.12 (d, J = 8.3 Hz,

Reference： [1]Patent: WO2020/47447,2020,A1 .Location in patent: Paragraph 0523

75
C₇H₆BrN [ No CAS ]
[ 66584-32-5 ]

Yield	Reaction Conditions	Operation in experiment
2.27 g	With methanol; sodium tetrahydroborate; at 0 - 80℃; for 2h;	3-Bromoaniline (5.00 g, 29.1 mmol) was dissolved in MeOH (90 mL), and NaOMe (11.25 g, 208 mmol) and paraformaldehyde (13.1 g, 437 mmol) were added and stirred overnight at room temperature. NaBH4 that had been cooled to 0 C. was added slowly, followed by stirring for two hours at 80 C. After adding 2N NaOH aqueous solution, extraction was performed by CH2C2; the organic layer was washed with saturated saline and dried with anhydrous Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc/n-hexane=), and N-methyl-3-bromoaniline was obtained (2.27 g, 12.4 mol, yield 42). (0241) 1H NMR (300 MHz, CDCl3): δ=2.81 (s, 3H), 3.78 (br, 1H), 6.51 (dd, J=8.1, 2.2 Hz, 1H), 6.73-6.74 (m, 1H), 6.80 (d, J=8.1 Hz, 1H), 6.99-7.04 (m, 1H). 13NMR (75 MHz, CDCl3): δ=30.5, 111.2, 114.7, 119.9, 123.3, 130.4, 150.5.

Reference： [1]Patent: US2020/87326,2020,A1 .Location in patent: Paragraph 0240-0241

76
[ 66584-32-5 ]
[ 920-46-7 ]
[ 1446402-76-1 ]

Reference： [1]Organic Letters,2020,vol. 22,p. 4583 - 4587
[2]Advanced Synthesis and Catalysis,2020,vol. 362,p. 5020 - 5025
[3]Journal of Organic Chemistry,2022,vol. 87,p. 4965 - 4970

77
(2S)-2-[(1H-indol-3-ylacetyl)amino]-3-phenylpropanoic acid [ No CAS ]
[ 66584-32-5 ]
(S)-2-(2-(1H-indol-3-yl)acetamido)-N-(3-bromophenyl)-N-methyl-3-phenylpropanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of indoleacetic acid derivative c (1 equiv.) in DMF(3 mL) were add HATU or T3P (2 equiv.) and DIPEA (3 equiv.), andthe mixture was stirred at room temperature for 20 min before anamine (1.2 equiv.) was added. The mixture was stirred at roomtemperature overnight. Upon completion of the reaction, H2O wasadded and the reaction mixture was extracted with EtOAc (3x20mL). The organic phases were combined and washed with brine,dried over anhydrous MgSO4, filtered and concentrated. Theproduct was purified by combi-flash on silica gel using EtOAc inhexane (yield 45e89%).

Reference： [1]European Journal of Medicinal Chemistry,2020,vol. 200

78
[ 67-56-1 ]
[ 585-79-5 ]
[ 66584-32-5 ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium tert-butylate; at 130℃; for 48h;Sealed tube;	General procedure: Nitroarenes (1.0mmol), 2a (7.9mg, 1mol %), KOtBu (112mg, 1.0 equiv.) were charged in a 15mL pressure tube with a magnetic bar. Then, 3.5mL of methanol was added into the mixture. The reaction tube was closed with the Teflon stopper and was heated to the desired temperature (130C) under stirring. After the desired reaction time, the reaction mixture was allowed to cool to room temperature. The solvent was removed under vacuum and then the product was purified by column chromatography and the product was analyzed by NMR spectroscopy.

Reference： [1]Journal of Catalysis,2020,vol. 389,p. 337 - 344
[2]Organometallics,2020,vol. 39,p. 3514 - 3523

79
[ 66584-32-5 ]
[ 79-44-7 ]
1-(3-bromophenyl)-1,3,3-trimethylurea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With dmap; triethylamine; In dichloromethane; at 0 - 50℃; for 120h;Schlenk technique; Inert atmosphere;	A 20 mL Schlenk tube, flame dried under vacuum and reflushed with argon, was charged with 69 μL(100 mg, 541 μmol, 1.0 eq) <strong>[66584-32-5]3-bromo-N-methylaniline</strong> dissolved in 2 mL abs. DCM. The clear reactionsolution was cooled to 0 C and 0.7 mg (5.41 μmol, 0.01 eq) DMAP as well as 151 μL (110 mg,1.08 mmol, 2.0 eq) abs. triethylamine were added. Then 75 μL (88 mg, 811 μmol, 1.5 eq)carbamoylchloride were added dropwise to the reaction solution. The reaction mixture was allowed towarm up to rt and was subsequently heated to 50 C. After 5 d GC-MS showed full conversion. Thereaction mixture was quenched by the addition of 1 mL dist. H2O and concentrated under reducedpressure. The brownish residue was resolved in 2 mL DCM and dried over MgSO4. The solvent wasremoved under reduced pressure. Purification via flash chromatography [CH/EE = 5/1, size: 10.0 x 1.5cm, 10 g SiO2] yielded the title compound as yellow oil (105 mg, 76 %).

Reference： [1]Bioorganic and medicinal chemistry,2020,vol. 28

80
[ 66584-32-5 ]
[ 541-41-3 ]
ethyl (3-bromophenyl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With dmap; triethylamine; In dichloromethane; at 0 - 50℃; for 72h;Schlenk technique; Inert atmosphere;	General procedure: A 20 mL Schlenk tube, flame dried under vacuum and reflushed with argon, was charged with 69 μL(100 mg, 541 μmol, 1.0 eq) <strong>[66584-32-5]3-bromo-N-methylaniline</strong> dissolved in 2 mL abs. DCM. The clear reactionsolution was cooled to 0 C and 0.7 mg (5.41 μmol, 0.01 eq) DMAP as well as 151 μL (110 mg,1.08 mmol, 2.0 eq) abs. triethylamine were added. Then 75 μL (88 mg, 811 μmol, 1.5 eq)carbamoylchloride were added dropwise to the reaction solution. The reaction mixture was allowed towarm up to rt and was subsequently heated to 50 C. After 5 d GC-MS showed full conversion. Thereaction mixture was quenched by the addition of 1 mL dist. H2O and concentrated under reducedpressure. The brownish residue was resolved in 2 mL DCM and dried over MgSO4. The solvent wasremoved under reduced pressure. Purification via flash chromatography [CH/EE = 5/1, size: 10.0 x 1.5cm, 10 g SiO2] yielded the title compound as yellow oil (105 mg, 76 %).

Reference： [1]Bioorganic and medicinal chemistry,2020,vol. 28

81
[ 66584-32-5 ]
[ 98-83-9 ]
C₁₆H₁₈BrN [ No CAS ]

Reference： [1]ACS Catalysis,2020,vol. 10,p. 6023 - 6029

82
[ 66584-32-5 ]
[ 13734-34-4 ]
C₂₁H₂₅BrN₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of commercially available (tert-butoxycarbonyl)-Lphenylalanine(1.0 g, 3.8 mmol, 1 equiv.) in DMF (5 mL), HATU or T3P (2 equiv.) andDIPEA (2 equiv.) were added and the mixture was stirred at room temperature for 20min before amine (1.5 equiv.) was added. The mixture was further stirred at roomtemperature overnight. Upon completion, H2O was added and the reaction mixture wasextracted with EtOAc (3x50 mL). The organic phases were combined and washed withbrine, dried over anhydrous MgSO4, filtered and concentrated. The product waspurified by Combi-flash on silica gel using EtOAc/hexane (1:4 to 2:1) as eluent.

Reference： [1]European Journal of Medicinal Chemistry,2020,vol. 204

83
[ 2985-33-3 ]
[ 66584-32-5 ]
ethyl 3-((3-bromophenyl)(methyl)amino)-2-methyl-3-oxopropanoate [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2020,vol. 2020,p. 6392 - 6398

84
[ 67-56-1 ]
[ 591-19-5 ]
[ 66584-32-5 ]
[ 16518-62-0 ]

Yield	Reaction Conditions	Operation in experiment
52%; 23%	With hydrogenchloride; cobalt(II,III) oxide; titanium(IV) oxide; In water; for 6h;UV-irradiation;	General procedure: A method for alkylation of aniline with Cu2O/TiO2 as a catalyst (loading amount is 0.01) and methanol as a carbon source, including the following processes:A 50 mL photoreaction flask with a stirrer was charged with 40 mL of methanol/water (water occupies 18% of the total volume of the reaction solvent (methanol+water)) solution, 250 mg of photocatalyst Cu2O/TiO, 5 mg of HCl and 0.2 mmol of substrate aniline.Then, the photoreaction flask was irradiated in a 365nm ultraviolet light source and stirred for 6 hours.Centrifuge the mixed solution system, add excess hydrochloric acid to adjust the pH to 1-2, and then rotate to evaporate all the methanol.The remaining aqueous reaction mixture was adjusted to pH 8 with sodium carbonate solution, and then extracted with water and ethyl acetate (5 times, 3 mL each time). The organic layer was washed with brine,Dry with Na2SO4 and evaporate to obtain a crude product.Distill and crystallize to obtain the product.The invention adopts a type II heterojunction photocatalyst, so that all the sub-steps of alkylation can be completed on the surface of the recombined catalyst under light conditions.After measurement, the final N-alkylation product yield was 99%, among which, the first-stage N-alkylation yield was 0.9%, and the second-stage N-alkylation yield was 99.1%. The results are shown in Table 1.

Reference： [1]Patent: CN112479894,2021,A .Location in patent: Paragraph 0048-0056; 0058

85
[ 66584-32-5 ]
[ 609769-63-3 ]
(E)-N-benzyl-N-(1-((3-bromophenyl)(methyl)amino)-2-phenylvinyl)-4-methylbenzenesulfonamide [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2021,vol. 86,p. 3433 - 3443

86
[ 1179348-58-3 ]
[ 66584-32-5 ]
C₁₆H₁₆BrNO₂ [ No CAS ]
C₁₆H₁₆BrNO₂ [ No CAS ]

Reference： [1]Chemical Science,2021,vol. 12,p. 7453 - 7459

87
[ 66584-32-5 ]
[ 121-45-9 ]
dimethyl (((3-bromophenyl)(methyl)amino)methyl)phosphonate [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2021,vol. 2021,p. 4278 - 4283

88
[ 66584-32-5 ]
C₁₂H₂₃N₃O₂ [ No CAS ]
[ 74-88-4 ]
C₁₈H₂₆BrN₃O₂ [ No CAS ]

Reference： [1]Chemical Science,2021,vol. 12,p. 9386 - 9390

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	66584-32-5	MDL No. :	MFCD05664376
Formula :	C₇H₈BrN	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HKOSFZXROYRVJT-UHFFFAOYSA-N
M.W :	186.05	Pubchem ID :	7018299
Synonyms :

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	1
Num. H-bond acceptors :	0.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.45
TPSA :	12.03 Å²

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) :	-5.59 cm/s

Log Po/w (iLOGP) :	2.03
Log Po/w (XLOGP3) :	2.6
Log Po/w (WLOGP) :	2.3
Log Po/w (MLOGP) :	2.57
Log Po/w (SILICOS-IT) :	2.2
Consensus Log Po/w :	2.34

[ CAS No. 66584-32-5 ] {[proInfo.proName]}

Quality Control of [ 66584-32-5 ]

Related Doc. of [ 66584-32-5 ]

Product Details of [ 66584-32-5 ]

Calculated chemistry of [ 66584-32-5 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 66584-32-5 ]

Application In Synthesis of [ 66584-32-5 ]

[ 66584-32-5 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 66584-32-5 ]

Aryls

Bromides

Amines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Log S (ESOL) :	-3.06
Solubility :	0.162 mg/ml ; 0.000873 mol/l
Class :	Soluble
Log S (Ali) :	-2.5
Solubility :	0.586 mg/ml ; 0.00315 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.69
Solubility :	0.0381 mg/ml ; 0.000205 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.5

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

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 66584-32-5 ] {[proInfo.proName]}

Quality Control of [ 66584-32-5 ]

Related Doc. of [ 66584-32-5 ]

Product Details of [ 66584-32-5 ]

Calculated chemistry of [ 66584-32-5 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 66584-32-5 ]

Application In Synthesis of [ 66584-32-5 ]

[ 66584-32-5 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 66584-32-5 ]

Aryls

Bromides

Amines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 66584-32-5 ]