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[ CAS No. 304858-65-9 ] {[proInfo.proName]}

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Quality Control of [ 304858-65-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 304858-65-9 ]

Product Details of [ 304858-65-9 ]

CAS No. :	304858-65-9	MDL No. :	MFCD08752638
Formula :	C₇H₅BrN₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PWJBXJQMHYIRKI-UHFFFAOYSA-N
M.W :	197.03	Pubchem ID :	9920636
Synonyms :

Calculated chemistry of [ 304858-65-9 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.26
TPSA :	49.81 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) :	-5.94 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.57
Log Po/w (XLOGP3) :	2.2
Log Po/w (WLOGP) :	1.91
Log Po/w (MLOGP) :	1.55
Log Po/w (SILICOS-IT) :	1.76
Consensus Log Po/w :	1.8

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.89
Solubility :	0.253 mg/ml ; 0.00128 mol/l
Class :	Soluble
Log S (Ali) :	-2.88
Solubility :	0.26 mg/ml ; 0.00132 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.98
Solubility :	0.206 mg/ml ; 0.00104 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.58

Safety of [ 304858-65-9 ]

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

Application In Synthesis of [ 304858-65-9 ]

* 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 [ 304858-65-9 ]
Downstream synthetic route of [ 304858-65-9 ]

[ 304858-65-9 ] Synthesis Path-Upstream 1~11

1
[ 304858-65-9 ]
[ 39859-36-4 ]

Reference： [1] Patent: US6498154, 2002, B1,

2
[ 304858-65-9 ]
[ 100-58-3 ]
[ 39859-36-4 ]

Reference： [1] Patent: US6358948, 2002, B1, . Location in patent: Example 17

3
[ 304858-65-9 ]
[ 122-51-0 ]
[ 21419-48-7 ]

Reference： [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 1, p. 305 - 309[2] Angew. Chem., 2014, vol. 126, # 1, p. 311 - 315,5

4
[ 304858-65-9 ]
[ 79603-03-5 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: at 0℃; for 0.166667 h; Cooling with ice Stage #2: at 0 - 50℃; for 2.5 h;	To a cold solution of trifluoroacetic acid (18 mL) at 0 °Cwas added compound 12 (4.5 g, 22.8 mmol). After beingstirred for 10 minutes, a solution of 33percent hydrogen peroxide(7 mL, 67.8 mmole) was added and the mixture was stirredat room temperature for 0.5 h followed by stirring at 50 °Cfor 2 h. The mixture was poured into ice water and the solidobtained was filtered and washed with cold water to afford3.64 g (70percent) of compound 18 as an off-white solid, m.p. 84-85 °C; IR (KBr) max. cm-1: 3042 (Ar-H), 2252 (CN), 1520,1412 (C=C). 1H NMR (500 MHz, DMSO-d6) = 8.15 (dd,1H, J = 2.4, 8.5 Hz, H-5); 8.25 (d, 1H, J = 8.4 Hz, H-6); 8.46(d, 1H, J = 2.4 Hz, H-3); 13C NMR (125.7 MHz, DMSO-d6) = 108.88 (C-1), 114.54 (CN), 127.43 (C-3), 128.75 (C-4),137.57 (C-5/C-6), 138.10 (C-5/C-6), 147.59 (C-2). Calculated(percent) for C7H3BrN2O2 (225.94); C: 37.03, H: 1.33, N:12.34, found (percent); C: 37.00, H: 1.37, N: 12.27.
70%	at 20 - 50℃;	Example 7 Synthesis of 4-Bromo-2-nitrobenzonitrile 17 To a cold solution of trifluoroacetic acid (18 mL) at 0° C. was added compound 8 (4.5 g, 23 mmol). After being stirred for 10 minutes, a solution of 33percent hydrogen peroxide (7 mL, 67.8 mmol) was added, and the mixture was stirred at room temperature for 0.5 h, followed by stirring at 50° C. for 2 h. The mixture was poured into ice water, and the solid obtained was filtered and washed with cold water to afford 3.64 g (70percent) of compound 17 as an off-white solid, m.p. 84-85° C.; IR (KBr) νmax. cm^-1: 3042 (Ar-H), 2252 (CN), 1520, 1412 (C=C). ¹H NMR (500 MHz, DMSO-d₆) δ=8.15 (dd, 1H, J=2.4, 8.5 Hz, H-5); 8.25 (d, 1H, J=8.4 Hz, H-6); 8.46 (d, 1H, J=2.4 Hz, H-3); ¹³C NMR (125.7 MHz, DMSO-d₆) δ=108.88 (C-1), 114.54 (CN), 127.43 (C-3), 128.75 (C-4), 137.57 (C-5/C-6), 138.10 (C-5/C-6), 147.59 (C-2). Calculated (percent) for C₇H₃BrN₂O₂(225.94); C, 37.03; H, 1.33; N, 12.34. found (percent); C, 37.00; H, 1.37; N, 12.27.

Reference： [1] Medicinal Chemistry, 2014, vol. 10, # 5, p. 484 - 496
[2] Patent: US8916704, 2014, B1, . Location in patent: Page/Page column 10

5
[ 304858-65-9 ]
[ 112253-70-0 ]

Reference： [1] Journal of Chemical Research, 2011, vol. 35, # 8, p. 480 - 483
[2] Patent: WO2010/56758, 2010, A1, . Location in patent: Page/Page column 118

6
[ 115049-55-3 ]
[ 304858-65-9 ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: With 2,6-dimethylpyridine; trifluoromethylsulfonic anhydride In dichloromethane at 0℃; for 3 h; Cooling with ice; Reflux Stage #2: With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20 - 30℃; for 1 h;	To a cold solution of oxime 11 (8 g, 33.19 mmol) inCH2Cl2 (200 mL) at 0 °C was added 2,6-lutidine (4.5 mL,38.8 mmol) followed by the dropwise addition of triflouromethanesulfonic anhydride (5.6 mL, 33.34 mmol). The cooling bath was removed and the mixture was heated toreflux for 3 h. The reaction mixture was cooled to room temperature and DBU (9.9 mL, 66.3 mmol) was added dropwis ewhile maintaining the internal temperature of the reaction below 30 °C. The mixture was further stirred at room temperature for 1 h and poured with vigorous stirring into excess dilute NaHCO3. This mixture was then stirred for several minutes and the organic layer was separated. The aqueous layer was re-extracted with CH2Cl2 (100 mL x 2). The combined extracts were dried with MgSO4 and concentrated to leave a dark brown solid, which was passed through a short silica column, eluting with CH2Cl2 (100percent). The resulting fraction was dried under vacuum, triturated with CH2Cl2 /hexanes (1:4; 50 mL) and solid formed was filtered and dried under vacuum to afford 5.36 g (82percent) of 12 as a light yellow solid. IR (KBr) max. cm-1: 3436, 3310 (NH2), 3032 (Ar-H),2920 (Alph-H), 2246 (CN), 1610, 1512, 1418 (C=C). 1HNMR (500 MHz, CDCl3) = 4.47 (br. s, 2H, NH2); 6.88 (dd,1H, J = 2.8, 8.2 Hz, H-5); 6.94 (br. s, 1H, H-3); 7.24 (d, 1H,J = 8.2 Hz, H-6); 13C NMR (125.7 MHz, CDCl3) = 95.17(C-1), 117.16 (CN), 118.15 (C-3), 121.60 (C-5), 129.03 (C-4), 133.60 (C-6), 150.47 (C-2). Calculated (percent) for C7H5BrN2(195.96); C: 42.67, H: 2.56, N: 14.22, found (percent); C: 42.60,H: 2.61, N: 14.17.
82%	Stage #1: With 2,6-dimethylpyridine; trifluoromethylsulfonic anhydride In dichloromethane at 0℃; for 3 h; Reflux Stage #2: With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20 - 30℃; for 1 h;	Example 2 Synthesis of 2-Amino-4-bromobenzonitrile 11 To a cold solution of oxime (10) (8 g, 33.33 mmol) in CH₂Cl₂ (200 mL) at 0° C. was added 2,6-lutidine (4.5 mL, 38.7 mmol), followed by the dropwise addition of trifluoromethanesulfonic anhydride (5.6 mL, 33.33 mmol). The cooling bath was removed, and the mixture was heated to reflux for 3 h. The reaction mixture was cooled to room temperature, and DBU (9.9 mL, 66.66 mmol) was added dropwise while maintaining the internal temperature of the reaction below 30° C. The mixture was further stirred at room temperature for 1 h and poured with vigorous stirring into excess dilute NaHCO₃. This mixture was then stirred for several minutes, and the organic layer was separated. The aqueous layer was re-extracted with CH₂Cl₂ (100 mL*2). The combined extracts were dried with MgSO₄ and concentrated to leave a dark brown solid, which was passed through a short silica column, eluting with CH₂Cl₂ (100percent). The resulting fraction was dried under vacuum, triturated with CH₂Cl₂/hexanes, and the solid formed was filtered and dried under vacuum to afford 5.36 g (82percent) of 11 as a light yellow solid. IR (KBr) νmax. cm^-1: 3436, 3310 (NH₂), 3032 (Ar-H), 2920 (Alph-H), 2246 (CN), 1610, 1512, 1418 (C=C). ¹H NMR (500 MHz, CDCl₃) δ=4.47 (br. s, 2H, NH₂); 6.88 (dd, 1H, J=2.8, 8.2 Hz, H-5); 6.94 (br. s, 1H, H-3); 7.24 (d, 1H, J=8.2 Hz, H-6); ¹³C NMR (125.7 MHz, CDCl₃) δ=95.17 (C-1), 117.16 (CN), 118.15 (C-3), 121.60 (C-5), 129.03 (C-4), 133.60 (C-6), 150.47 (C-2). Calculated (percent) for C₇H₅BrN₂ (195.96); C, 42.67; H, 2.56; N, 14.22. found (percent); C, 42.60; H, 2.61; N, 14.17.

Reference： [1] Medicinal Chemistry, 2014, vol. 10, # 5, p. 484 - 496
[2] Patent: US8916704, 2014, B1, . Location in patent: Page/Page column 8

7
[ 1885-29-6 ]
[ 304858-65-9 ]

Reference： [1] Canadian Journal of Chemistry, 2005, vol. 83, # 2, p. 146 - 149

8
[ 591-19-5 ]
[ 304858-65-9 ]

Reference： [1] Medicinal Chemistry, 2014, vol. 10, # 5, p. 484 - 496

9
[ 65971-74-6 ]
[ 304858-65-9 ]

Reference： [1] Medicinal Chemistry, 2014, vol. 10, # 5, p. 484 - 496

10
[ 6326-79-0 ]
[ 304858-65-9 ]

Reference： [1] Medicinal Chemistry, 2014, vol. 10, # 5, p. 484 - 496

11
[ 304858-65-9 ]
[ 1207175-68-5 ]

Reference： [1] Medicinal Chemistry, 2014, vol. 10, # 5, p. 484 - 496
[2] Patent: US8916704, 2014, B1,

[ 304858-65-9 ] Synthesis Path-Downstream 1~88

1
[ 1885-29-6 ]
[ 304858-65-9 ]

Reference： [1]Canadian Journal of Chemistry,2005,vol. 83,p. 146 - 149

2
[ 304858-65-9 ]
[ 100-58-3 ]
[ 39859-36-4 ]

Reference： [1]Patent: US6358948,2002,B1 .Location in patent: Example 17

3
[ 304858-65-9 ]
aqueous hydrogen chloride [ No CAS ]
[ 39859-36-4 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; ethyl acetate;	EXAMPLE 17 3-[(2R,4S)-2,4-Dimethyl-4-phenyl-1,4-dihydro-2H-3,1-benzoxazin-6-yl]-5-fluorobenzonitrile To a solution of <strong>[304858-65-9]2-amino-4-bromobenzonitrile</strong> (5 g, 25 mmol) in anhydrous THF, was added at 0 C. under nitrogen, phenylmagnesium bromide (3 M in ether, 25 mL, 75 mmol). The mixture was allowed to warm to room temperature, stirred under nitrogen for 15 hours, and treated with 2N aqueous hydrogen chloride solution (100 mL). The aqueous solution was heated to 50 C. for 3 hours, cooled to room temperature, and neutralized with a cold saturated sodium bicarbonate solution. Ethyl acetate (100 mL) was added and the organic layer was separated and aqueous layer was extracted with ethyl acetate (3*40 mL). The combined organic layers were dried (MgSO4) and evaporated. The residue was purified by a flash column chromatography(silica gel, hexane:ethyl acetate/4:1) to yield (2-amino-5-bromophenyl)(phenyl)methanone as a yellow crystal (2.13 g, 31%): MS (ESI) m/z 276/278 (M+H)+.

Reference： [1]Patent: US6498154,2002,B1

4
[ 304858-65-9 ]
[ 585-07-9 ]
[ 1297552-95-4 ]

Reference： [1]Patent: US2011/130445,2011,A1

5
[ 304858-65-9 ]
[ 585-07-9 ]
[ 1297552-93-2 ]

Yield	Reaction Conditions	Operation in experiment
52%	With N-Methyldicyclohexylamine;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In 1,4-dioxane; at 120℃;Inert atmosphere;	Example 223Atert-Butyl(2E)-3-(3-amino-4-cyanophenyl)-2-methylacrylate; Under argon, a mixture of 2.0 g (10.15 mmol) of <strong>[304858-65-9]2-amino-4-bromobenzonitrile</strong>, 2.165 g (2.5 ml, 15.23 mmol) of tert-butyl 2-methylacrylate, 93 mg (0.10 mmol) of tris(dibenzylideneacetone)-dipalladium, 41 mg (0.20 mmol) of tri-tert-butylphosphine and 2.4 ml (11.17 mmol) of N,N-di-cyclohexylmethylamine in 20 ml of dioxane was heated to 120 C. and stirred at this temperature overnight. The reaction was checked (TLC, mobile phase cyclohexane/ethyl acetate 9:1), and another 10 mg of tris(dibenzylideneacetone)dipalladium, 10 mg of tri-tert-butylphosphine and 500 mul of tert-butyl 2-methylacrylate were then added and the mixture was stirred at 120 C. for a further 4 h. The reaction mixture was then filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethylacetate 9:1?4:1). This gave 1.375 g of the title compound (52% of theory).LC-MS (Method 4): Rt=1.33 min; m/z=259 (M+H)+.

Reference： [1]Patent: US2011/130445,2011,A1 .Location in patent: Page/Page column 89

6
[ 304858-65-9 ]
C₁₀H₇BrN₄S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3738 - 3742

7
[ 304858-65-9 ]
[ 463-71-8 ]
C₈H₃BrN₂S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3738 - 3742

8
[ 304858-65-9 ]
[ 1536086-92-6 ]

Reference： [1]Angewandte Chemie - International Edition,2014,vol. 53,p. 305 - 309
Angew. Chem.,2014,vol. 126,p. 311 - 315,5

9
[ 304858-65-9 ]
[ 78-39-7 ]
[ 1536086-83-5 ]

Reference： [1]Angewandte Chemie - International Edition,2014,vol. 53,p. 305 - 309
Angew. Chem.,2014,vol. 126,p. 311 - 315,5

10
[ 591-19-5 ]
[ 304858-65-9 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

11
[ 65971-74-6 ]
[ 304858-65-9 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

12
[ 6326-79-0 ]
[ 304858-65-9 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

13
[ 115049-55-3 ]
[ 304858-65-9 ]

Yield	Reaction Conditions	Operation in experiment
82%		To a cold solution of oxime 11 (8 g, 33.19 mmol) inCH2Cl2 (200 mL) at 0 C was added 2,6-lutidine (4.5 mL,38.8 mmol) followed by the dropwise addition of triflouromethanesulfonic anhydride (5.6 mL, 33.34 mmol). The cooling bath was removed and the mixture was heated toreflux for 3 h. The reaction mixture was cooled to room temperature and DBU (9.9 mL, 66.3 mmol) was added dropwis ewhile maintaining the internal temperature of the reaction below 30 C. The mixture was further stirred at room temperature for 1 h and poured with vigorous stirring into excess dilute NaHCO3. This mixture was then stirred for several minutes and the organic layer was separated. The aqueous layer was re-extracted with CH2Cl2 (100 mL x 2). The combined extracts were dried with MgSO4 and concentrated to leave a dark brown solid, which was passed through a short silica column, eluting with CH2Cl2 (100%). The resulting fraction was dried under vacuum, triturated with CH2Cl2 /hexanes (1:4; 50 mL) and solid formed was filtered and dried under vacuum to afford 5.36 g (82%) of 12 as a light yellow solid. IR (KBr) max. cm-1: 3436, 3310 (NH2), 3032 (Ar-H),2920 (Alph-H), 2246 (CN), 1610, 1512, 1418 (C=C). 1HNMR (500 MHz, CDCl3) = 4.47 (br. s, 2H, NH2); 6.88 (dd,1H, J = 2.8, 8.2 Hz, H-5); 6.94 (br. s, 1H, H-3); 7.24 (d, 1H,J = 8.2 Hz, H-6); 13C NMR (125.7 MHz, CDCl3) = 95.17(C-1), 117.16 (CN), 118.15 (C-3), 121.60 (C-5), 129.03 (C-4), 133.60 (C-6), 150.47 (C-2). Calculated (%) for C7H5BrN2(195.96); C: 42.67, H: 2.56, N: 14.22, found (%); C: 42.60,H: 2.61, N: 14.17.
82%		Example 2 Synthesis of 2-Amino-4-bromobenzonitrile 11 To a cold solution of oxime (10) (8 g, 33.33 mmol) in CH2Cl2 (200 mL) at 0 C. was added 2,6-lutidine (4.5 mL, 38.7 mmol), followed by the dropwise addition of trifluoromethanesulfonic anhydride (5.6 mL, 33.33 mmol). The cooling bath was removed, and the mixture was heated to reflux for 3 h. The reaction mixture was cooled to room temperature, and DBU (9.9 mL, 66.66 mmol) was added dropwise while maintaining the internal temperature of the reaction below 30 C. The mixture was further stirred at room temperature for 1 h and poured with vigorous stirring into excess dilute NaHCO3. This mixture was then stirred for several minutes, and the organic layer was separated. The aqueous layer was re-extracted with CH2Cl2 (100 mL*2). The combined extracts were dried with MgSO4 and concentrated to leave a dark brown solid, which was passed through a short silica column, eluting with CH2Cl2 (100%). The resulting fraction was dried under vacuum, triturated with CH2Cl2/hexanes, and the solid formed was filtered and dried under vacuum to afford 5.36 g (82%) of 11 as a light yellow solid. IR (KBr) numax. cm-1: 3436, 3310 (NH2), 3032 (Ar-H), 2920 (Alph-H), 2246 (CN), 1610, 1512, 1418 (C=C). 1H NMR (500 MHz, CDCl3) delta=4.47 (br. s, 2H, NH2); 6.88 (dd, 1H, J=2.8, 8.2 Hz, H-5); 6.94 (br. s, 1H, H-3); 7.24 (d, 1H, J=8.2 Hz, H-6); 13C NMR (125.7 MHz, CDCl3) delta=95.17 (C-1), 117.16 (CN), 118.15 (C-3), 121.60 (C-5), 129.03 (C-4), 133.60 (C-6), 150.47 (C-2). Calculated (%) for C7H5BrN2 (195.96); C, 42.67; H, 2.56; N, 14.22. found (%); C, 42.60; H, 2.61; N, 14.17.

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496
[2]Patent: US8916704,2014,B1 .Location in patent: Page/Page column 8

14
[ 304858-65-9 ]
[ 1630951-35-7 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

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[ 304858-65-9 ]
[ 1630951-36-8 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

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[ 304858-65-9 ]
[ 1630951-37-9 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

17
[ 304858-65-9 ]
[ 1630951-38-0 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

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[ 304858-65-9 ]
[ 1630951-39-1 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

19
[ 304858-65-9 ]
[ 1630951-40-4 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

20
[ 304858-65-9 ]
[ 1630951-41-5 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

21
[ 304858-65-9 ]
[ 1630951-42-6 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

22
[ 304858-65-9 ]
[ 624813-49-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	With borane-THF; In tetrahydrofuran; at 0 - 20℃; for 72h;Inert atmosphere;	To a solution of compound 12 (2 g, 10.1 mmol) in dryTHF at 0 C under an argon atmosphere was slowly added borane (15 mL, 1.0 M in THF). The reaction mixture wasstirred for 10 min at 0 C and further 72 h at room temperature.The reaction mixture was cooled to 0 C and quenchedby addition of ethanol (96%). The resulting suspension wasextracted with ethyl acetate (3 20 mL). The combined organiclayers were dried over sodium sulfate. Ethyl acetatewas completely removed under reduced pressure and theresidues were chromatographed over silica column, elutingwith ethyl acetate:hexanes (1:1) and changing to (100%)afforded 1.73 g (85%) of compound 13 as a dark brown thickgum. IR (KBr) max. cm-1: 3438, 3318 (NH2), 3052 (Ar-H),2911 (Alph-H), 1604, 1512, 1416 (C=C). 1H NMR (500MHz, CDCl3) = 4.19 (br. s, 2H, NH2); 4.42 (s, 2H, CH2);6.52 (d, 1H, J = 8.2 Hz, H-3); 7.16 (dd, 1H, J = 2.2, 8.2 Hz,H-4); 7.18 (d, 1H, J = 2.2 Hz, H-6); 13C NMR (125.7 MHz,CDCl3) = 63.78 (CH2), 109.56 (C-2), 117.51 (C-6), 126.57(C-5), 131.58 (C-3/C-4), 131.86 (C-3/C-4), 145.06 (C-1).Calculated (%) for C7H9BrN2 (199.99); C: 41.82, H: 4.51, N:13.93, found (%); C: 41.74, H: 4.58, N: 13.84.
85%	With borane-THF; In tetrahydrofuran; at 0 - 20℃; for 72h;Inert atmosphere;	Example 3 Synthesis of 2-(Aminomethyl)-5-bromoaniline 12 To a solution of compound (II) (2 g, 10.0 mmol) in dry THF at 0 C. under an argon atmosphere was slowly added borane (15 mL, 1.0 M in THF). The reaction mixture was stirred for 10 min at 0 C. and further 72 h at room temperature. The reaction mixture was cooled to 0 C. and quenched by addition of ethanol (96%). The resulting suspension was extracted with ethyl acetate (3*20 mL). The combined organic layers were dried over sodium sulfate. Ethyl acetate was completely removed under reduced pressure and the residues were chromatographed over silica column, eluting with ethyl acetate:hexanes (1:1) and changing to (100%) afforded 1.73 g (85%) of compound (12) as a dark brown thick gum. IR (KBr) numax. cm-1: 3438, 3318 (NH2), 3052 (Ar-H), 2911 (Alph-H), 1604, 1512, 1416 (C=C). 1H NMR (500 MHz, CDCl3) delta=4.19 (br. s, 2H, NH2); 4.42 (s, 2H, CH2); 6.52 (d, 1H, J=8.2 Hz, H-3); 7.16 (dd, 1H, J=2.2, 8.2 Hz, H-4); 7.18 (d, 1H, J=2.2 Hz, H-6); 13C NMR (125.7 MHz, CDCl3) delta=63.78 (CH2), 109.56 (C-2), 117.51 (C-6), 126.57 (C-5), 131.58 (C-3/C-4), 131.86 (C-3/C-4), 145.06 (C-1). Calculated (%) for C7H9BrN2 (199.99); C, 41.82; H, 4.51; N, 13.93. found (%); C, 41.74; H, 4.58; N, 13.84.

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496
[2]Patent: US8916704,2014,B1 .Location in patent: Page/Page column 9

23
[ 304858-65-9 ]
[ 1630951-18-6 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496
[2]Patent: US8916704,2014,B1

24
[ 304858-65-9 ]
[ 1207175-68-5 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496
[2]Patent: US8916704,2014,B1

25
[ 304858-65-9 ]
[ 1630951-16-4 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496
[2]Patent: US8916704,2014,B1

26
[ 304858-65-9 ]
[ 1630951-19-7 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

27
[ 304858-65-9 ]
[ 79603-03-5 ]

Yield	Reaction Conditions	Operation in experiment
70%		To a cold solution of trifluoroacetic acid (18 mL) at 0 Cwas added compound 12 (4.5 g, 22.8 mmol). After beingstirred for 10 minutes, a solution of 33% hydrogen peroxide(7 mL, 67.8 mmole) was added and the mixture was stirredat room temperature for 0.5 h followed by stirring at 50 Cfor 2 h. The mixture was poured into ice water and the solidobtained was filtered and washed with cold water to afford3.64 g (70%) of compound 18 as an off-white solid, m.p. 84-85 C; IR (KBr) max. cm-1: 3042 (Ar-H), 2252 (CN), 1520,1412 (C=C). 1H NMR (500 MHz, DMSO-d6) = 8.15 (dd,1H, J = 2.4, 8.5 Hz, H-5); 8.25 (d, 1H, J = 8.4 Hz, H-6); 8.46(d, 1H, J = 2.4 Hz, H-3); 13C NMR (125.7 MHz, DMSO-d6) = 108.88 (C-1), 114.54 (CN), 127.43 (C-3), 128.75 (C-4),137.57 (C-5/C-6), 138.10 (C-5/C-6), 147.59 (C-2). Calculated(%) for C7H3BrN2O2 (225.94); C: 37.03, H: 1.33, N:12.34, found (%); C: 37.00, H: 1.37, N: 12.27.
70%	With dihydrogen peroxide; trifluoroacetic acid; at 20 - 50℃;	Example 7 Synthesis of 4-Bromo-2-nitrobenzonitrile 17 To a cold solution of trifluoroacetic acid (18 mL) at 0 C. was added compound 8 (4.5 g, 23 mmol). After being stirred for 10 minutes, a solution of 33% hydrogen peroxide (7 mL, 67.8 mmol) was added, and the mixture was stirred at room temperature for 0.5 h, followed by stirring at 50 C. for 2 h. The mixture was poured into ice water, and the solid obtained was filtered and washed with cold water to afford 3.64 g (70%) of compound 17 as an off-white solid, m.p. 84-85 C.; IR (KBr) numax. cm-1: 3042 (Ar-H), 2252 (CN), 1520, 1412 (C=C). 1H NMR (500 MHz, DMSO-d6) delta=8.15 (dd, 1H, J=2.4, 8.5 Hz, H-5); 8.25 (d, 1H, J=8.4 Hz, H-6); 8.46 (d, 1H, J=2.4 Hz, H-3); 13C NMR (125.7 MHz, DMSO-d6) delta=108.88 (C-1), 114.54 (CN), 127.43 (C-3), 128.75 (C-4), 137.57 (C-5/C-6), 138.10 (C-5/C-6), 147.59 (C-2). Calculated (%) for C7H3BrN2O2(225.94); C, 37.03; H, 1.33; N, 12.34. found (%); C, 37.00; H, 1.37; N, 12.27.

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496
[2]Patent: US8916704,2014,B1 .Location in patent: Page/Page column 10

28
[ 304858-65-9 ]
[ 1027345-15-8 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496
[2]Patent: US8916704,2014,B1

29
[ 304858-65-9 ]
[ 1630951-20-0 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496
[2]Patent: US8916704,2014,B1

30
[ 304858-65-9 ]
[ 1630951-21-1 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496
[2]Patent: US8916704,2014,B1

31
[ 304858-65-9 ]
[ 1630951-24-4 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496
[2]Patent: US8916704,2014,B1

32
[ 304858-65-9 ]
[ 1630951-25-5 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496
[2]Patent: US8916704,2014,B1

33
[ 304858-65-9 ]
[ 1630951-27-7 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

34
[ 304858-65-9 ]
[ 1630951-28-8 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

35
[ 304858-65-9 ]
[ 1630951-23-3 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

36
[ 304858-65-9 ]
[ 1630951-30-2 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

37
[ 304858-65-9 ]
[ 1630951-31-3 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

38
[ 304858-65-9 ]
[ 1630951-32-4 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

39
[ 304858-65-9 ]
[ 1630951-33-5 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

40
[ 304858-65-9 ]
[ 1630951-34-6 ]

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

41
[ 304858-65-9 ]
[ 375853-82-0 ]
[ 1630951-26-6 ]

Yield	Reaction Conditions	Operation in experiment
72%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 14h;Inert atmosphere;	General procedure: To a nitrogen flushed flask containing the boronate 22(1.39 g, 4.5 mmol), KOAc (1.86 g, 13.5 mmol) andPdCl2dppf (0.23 g, 0.28 mmol) was added a solution of thebromide 14 (1.07 g, 4.7 mmol) in DMF (30 mL). The mixturewas deoxygenated by continued flushing with nitrogen.The mixture was then heated to 80C and stirred under N2overnight when TLC indicated completion of the reaction.After cooling ethyl acetate (40 mL) and water (20 mL) wereadded and the organic phase was separated. The water phasewas extracted with ethyl acetate (20 mL). The combinedorganic phases were washed with brine, dried over Na2SO4,filtered over a short plug of celite and evaporated under reducedpressure. Column chromatography on silica gel,eluting with hexanes:ethyl acetate (6:4) and then changing to(4:6)) afforded 0.39 g (28%) of compound 23 as an off-whitesolid, m.p. 183-184 C; IR (KBr) max. cm-1: 3261, 3155(NH), 3052 (Ar-H), 1695 (C=O), 1616, 1518, 1415 (C=C).1H-NMR (500 MHz, CDCl3) = 1.49 (s, 9H, (CH3)3C); 1.72(br. s, 2H, CH2); 2.47 (br. s, 2H, CH2); 3.63 (m, 2H, CH2);4.07 (s, 2H, CH2); 5.97 (br. s, 1H, CH); 6.76 (d, J = 8.2 Hz,1H, H-5); 7.12 (br. s, 1H, H-8); 7.28 (m, 1H, H-6); 7.65 (br.s, 1H, NH); 13C NMR (125.7 MHz, CDCl3) = 27.39 (CH2),28.48 (CH3)3C), 29.71 (CH2), 41.90 (CH2), 68.73 (CH2),79.80 (CH3)3C), 113.87 (aromatic-C), 118.03 (aromatic-C),120.92 (aromatic-C), 125.75 (aromatic-C), 134.49 (aromatic-C), 136.34 (aromatic-C), 152.59 (C=O), 154. 88 (C=O). Calculated(%) for C18H23N3O3 (329.17); C: 65.63, H: 7.04, N:12.76, found (%); C: 65.57, H: 7.09, N: 12.69.

Reference： [1]Medicinal Chemistry,2014,vol. 10,p. 484 - 496

42
[ 304858-65-9 ]
C₁₂H₁₁BrN₂O [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 5376 - 5380
[2]Synthesis,2018,vol. 50,p. 3460 - 3466
[3]European Journal of Organic Chemistry,2019,vol. 2019,p. 5749 - 5755

43
[ 304858-65-9 ]
C₂₄H₂₁BrNO₃P [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 5376 - 5380

44
[ 304858-65-9 ]
[ 920-46-7 ]
C₁₁H₉BrN₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 0 - 20℃;	General procedure: To the solution of anthranilonitrile S-1 (2.0 mmol) and Et3N (2.4 mmol) in 20 mL dry CH2Cl2 was added acryloyl chloride (2.2 mmol) at 0 C. The mixture was allowed to stir at room temperature. After completion of the reaction, the reaction was quenched with saturated NaHCO3 solution, then extracted with CH2Cl2, washed with brine, dried over MgSO4 and concentrated by evaporator affording amide S-2 without any further purification.

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 5376 - 5380
[2]Synthesis,2018,vol. 50,p. 3460 - 3466
[3]European Journal of Organic Chemistry,2019,vol. 2019,p. 5749 - 5755

45
[ 304858-65-9 ]
[ 541-41-3 ]
ethyl (5-bromo-2-cyanophenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	for 6h;Reflux;	General procedure: In a 50 mL round bottom flask, a suspension of 2-aminoarylnitriles (10.0 mmol) in ethyl chloroformate(52.0 mmol, 5.0 mL) was refluxing for 6 h. After complete removal of excess ethyl chloroformate in vacuo (by forming azeotrope with toluene), the residue was recrystallized from cyclohexane (for mostsubstrates) to furnish the title compound.

Reference： [1]Tetrahedron Letters,2015,vol. 56,p. 5429 - 5433

46
[ 304858-65-9 ]
ethyl 5-amino-9-bromo-11H-indolo[3,2-c]isoquinoline-11-carboxylate [ No CAS ]

Reference： [1]Tetrahedron Letters,2015,vol. 56,p. 5429 - 5433

47
[ 304858-65-9 ]
C₁₈H₁₄BrN₃O₂ [ No CAS ]

Reference： [1]Tetrahedron Letters,2015,vol. 56,p. 5429 - 5433

48
[ 304858-65-9 ]
[ 1885-29-6 ]
7-bromo-2-phenylquinazolin-4(3H)-one [ No CAS ]

Reference： [1]ChemCatChem,2016,vol. 8,p. 1523 - 1530

49
[ 304858-65-9 ]
[ 20769-85-1 ]
2-bromo-N-(5-bromo-2-cyanophenyl)-2-methylpropanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 1.08333h;	To a solution of <strong>[304858-65-9]2-amino-4-bromobenzonitrile</strong> (1.02 g, 5.18 mmol) and N-ethylN-isopropylpropan-2-amine (1.353 ml, 7.77 mmol) in DCM (24.65 ml), cooled to 0 C, was added 2-bromo-2-methylpropanoyl bromide (0.83 2 ml, 6.73 mmol) slowly. Thereaction mixture was stirred at 0 C for 5 mm, then at room temperature for 1 h. The reaction was monitored by LCMS. The reaction mixture was diluted with DCM and washed with 1 N HC1. The organic phase was washed with 1 .5M K2HPO4, brine, dried by Na2SO4. The solvent was removed under reduced pressure affording 2-bromo-N-(5- bromo-2-cyanophenyl)-2-methylpropanamide (2.19 g) as a pale solid in quantitativeyield. LCMS M+H = 344.9, 346.9, and 348.9.

Reference： [1]Patent: WO2016/64957,2016,A1 .Location in patent: Page/Page column 181
[2]Journal of Medicinal Chemistry,2017,vol. 60,p. 5193 - 5208

50
[ 304858-65-9 ]
N-(5-bromo-2-cyanophenyl)-2-((2-hydroxyethyl)amino)-2-methylpropanamide [ No CAS ]

Reference： [1]Patent: WO2016/64957,2016,A1
[2]Journal of Medicinal Chemistry,2017,vol. 60,p. 5193 - 5208

51
[ 304858-65-9 ]
4-bromo-2-(3,3-dimethyl-2-oxopiperazin-1-yl)benzonitrile [ No CAS ]

Reference： [1]Patent: WO2016/64957,2016,A1
[2]Journal of Medicinal Chemistry,2017,vol. 60,p. 5193 - 5208

52
[ 304858-65-9 ]
2-(4-acetyl-3,3-dimethyl-2-oxopiperazin-1-yl)-4-bromobenzonitrile [ No CAS ]

Reference： [1]Patent: WO2016/64957,2016,A1
[2]Journal of Medicinal Chemistry,2017,vol. 60,p. 5193 - 5208

53
[ 304858-65-9 ]
C₂₂H₂₁F₃N₆O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2849 - 2853

54
[ 304858-65-9 ]
C₁₅H₁₉BrN₂O₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2849 - 2853

55
[ 304858-65-9 ]
C₁₅H₁₉BN₂O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2849 - 2853

56
[ 304858-65-9 ]
C₁₅H₁₇BrN₂O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2849 - 2853

57
[ 304858-65-9 ]
2-bromo-2-methylpropanoyl halide [ No CAS ]
2-bromo-N-(5-bromo-2-cyanophenyl)-2-methylpropanamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2849 - 2853

58
[ 304858-65-9 ]
C₁₄H₁₈BrN₃O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5193 - 5208

59
[ 304858-65-9 ]
C₁₄H₁₈BrN₃O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5193 - 5208

60
[ 304858-65-9 ]
C₁₄H₁₆BrN₃O [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5193 - 5208

61
[ 304858-65-9 ]
C₁₄H₁₆BrN₃O [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5193 - 5208

62
[ 304858-65-9 ]
C₁₆H₁₈BrN₃O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5193 - 5208

63
[ 304858-65-9 ]
C₁₆H₁₈BrN₃O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5193 - 5208

64
[ 304858-65-9 ]
[ 79-22-1 ]
[ 100-58-3 ]
7-bromo-4-phenylquinazolin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%		General procedure: All glassware was oven dried overnight and anhydrous solvent was obtained from an Innovative Technology Pure Solvent system. A solution of phenyl magnesium bromide in diethyl ether (13.3 mL of a 3.0 M solution, 40 mmol, 2 eq.) was added via syringe to a stirred, room temperature solution of <strong>[304858-65-9]2-amino-5-bromobenzonitrile</strong> (3.94 g, 20 mmol, 1 eq.) in anhydrous THF (30 mL) under a nitrogen atmosphere. The reaction mixture was heated at 70 C with stirring for 2 h, then cooled to room temperature and placed on an ice water bath. Methyl chloroformate (3.87 mL, 50 mmol, 2.5 eq.) was then added slowly dropwise via syringe. The reactions mixture was then heated to 70 C with stirring for 3 h, and then maintained at room temperature for an additional 12 h. A solution of aqueous HCl (2 M, 40 mL) was added and the mixture was allowed to stir for 5 min. Saturated aqueous sodium bicarbonate was then added to neutralize the reaction mixture, which was then placed on ice water bath for 20 min. The resulting precipitate was then filtered through a fritted funnel and washed with H2O (10 mL) followed by diethyl ether (5 mL) to give 4a (4.92 g, 82% yield), which was used without further purification unless otherwise noted.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3629 - 3635

65
[ 304858-65-9 ]
4-phenyl-7-(pyridin-4-yl)quinazolin-2(1H)-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3629 - 3635

66
[ 304858-65-9 ]
4-phenyl-7-(pyridin-3-yl)quinazolin-2(1H)-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3629 - 3635

67
[ 304858-65-9 ]
4-phenyl-7-(pyrimidin-5-yl)quinazolin-2(1H)-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3629 - 3635

68
[ 304858-65-9 ]
7-[3-(morpholin-4-yl)phenyl]-4-phenylquinazolin-2(1H)-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3629 - 3635

69
[ 304858-65-9 ]
7-(4-fluorophenyl)-4-phenylquinazolin-2(1H)-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3629 - 3635

70
[ 304858-65-9 ]
[ 17159-79-4 ]
ethyl 9-amino-6-bromo-1,2,3,4-tetrahydroacridine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With boron trifluoride diethyl etherate; In toluene; at 100 - 110℃;	To a solution of 2-amino-4-cyano-benzonitrile 1 (5.0 g, 0.0253 mol, 1.0 eqiv) in anhydrous toluene was added BF3.Et20 (3.76 mL, 0.0304 mol, 1.2 eqiv) slowly at room temperature. The reaction mixture was cooled to 0C followed by the addition of ethyl-4-oxocyclohexanecarboxylate (6.4 mL, 0.0379, 1.5 eqiv) and the reaction mixture was heated to l00C for 4 h. After completion, the reaction was monitored by TLC, the reaction mixture was quenched with aq. NaOH solution up to pH= 10 and the reaction mixture was diluted with ethyl acetate. The organic layers were separated, dried over sodium sulphate and concentrated. The crude product was recrystallized from dichloromethane to obtain ethyl 9-amino-6- bromo-l,2,3,4-tetrahydroacridine-2-carboxylate (05) (7.0 g, 85%) as off white solid. (0130) *H NMR (400 MHz, DMSO-d6): d 8.13 (d, lH,/= 8.96 Hz), 7.79 (s, 1H), 7.40 (dd, 1H, J= 8.92, 8.92 Hz), 6.61 (s, 2H), 4.19-4.07 (m, 2H), 2.94-2.85 (m, 4H), 2.68-2.61 (m, 1H), 2.l5-2.l l(m, 1H), 1.89-1.80 (m, 1H), 1.24 (t, 3H, /= 7.12 Hz). LCMS: 351.7 (M+2), m/z calculated for Ci6H17BrN202.
84%	With boron trifluoride diethyl etherate; In toluene; at 0 - 100℃; for 4h;	General procedure: An oven dried RB flask was charged with 2-aminobenzonitrille1a(3 g, 25.4 mmol) in anhydrous toluene (30 mL).BF3.Et2O (3.2 ml, 30.48 mmol) was added slowly at room temperature.The reaction contents were cooled to 0 C followed by thedrop wise addition of ethyl-4-oxocyclohexanecarboxylate (8.0 mL,50.8 mmol). The reaction contents were then refluxed to 100 C for4 h. After completion of the reaction as indicated by TLC, the reactionmixture was quenched with aq. NaOH solution to adjust thepH to around 12 and the reaction mixture was diluted with ethylacetate.The organic layers were then separated, dried over anhydrous sodium sulphate, filtered and concentrated to obtain thecrude material which was recrystallized from dichloromethane toyield the product 3a.

Reference： [1]Patent: WO2019/207604,2019,A1 .Location in patent: Paragraph 0038
[2]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

71
[ 304858-65-9 ]
9-amino-6-bromo-N-phenethyl-1,2,3,4-tetrahydroacridine-2-carboxamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

72
[ 304858-65-9 ]
9-amino-6-bromo-N-(3-phenylpropyl)-1,2,3,4-tetrahydroacridine-2-carboxamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

73
[ 304858-65-9 ]
9-amino-6-(1-methyl-1H-pyrazol-4-yl)-1,2,3,4-tetrahydroacridine-2-carboxylic acid benzylamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

74
[ 304858-65-9 ]
9-amino-6-(1-methyl-1H-pyrazol-4-yl)-N-phenethyl-1,2,3,4-tetrahydroacridine-2-carboxamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

75
[ 304858-65-9 ]
9-amino-6-(1-methyl-1H-pyrazol-4-yl)-N-(3-phenylpropyl)-1,2,3,4-tetrahydroacridine-2-carboxamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

76
[ 304858-65-9 ]
9-amino-N-(3-phenylpropyl)-6-(pyrimidin-5-yl)-1,2,3,4-tetrahydroacridine-2-carboxamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

77
[ 304858-65-9 ]
C₂₁H₂₀BrN₃O [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

78
[ 304858-65-9 ]
C₁₅H₁₆BrN₃O [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

79
[ 304858-65-9 ]
ethyl 9-amino-6-(1-methyl-1H-pyrazol-4-yl)-1,2,3,4-tetrahydroacridine-2-carboxylate [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377
[2]Patent: WO2019/207604,2019,A1

80
[ 304858-65-9 ]
C₂₀H₂₀N₄O₂ [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

81
[ 304858-65-9 ]
C₁₈H₁₆N₄O₂ [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

82
[ 304858-65-9 ]
9-amino-6-bromo-1,2,3,4-tetrahydroacridine-2-carbohydrazide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

83
[ 304858-65-9 ]
9-amino-6-bromo-1,2,3,4-tetrahydroacridine-2-carboxylic acid [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

84
[ 304858-65-9 ]
9-amino-6-(1-methyl-1H-pyrazol-4-yl)-1,2,3,4-tetrahydroacridine-2-carboxylic acid [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 139,p. 367 - 377

85
[ 304858-65-9 ]
[ 100-58-3 ]
[ 135776-98-6 ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 13927 - 13930
Angew. Chem.,2018,vol. 130,p. 14123 - 14126,4
[2]Organic Letters,2017,vol. 19,p. 5292 - 5295

86
[ 304858-65-9 ]
(4-bromo-2-isocyanophenyl)(phenyl)methanone [ No CAS ]

Reference： [1]Organic Letters,2017,vol. 19,p. 5292 - 5295

87
[ 304858-65-9 ]
C₁₄H₁₀BrNO₂ [ No CAS ]

Reference： [1]Organic Letters,2017,vol. 19,p. 5292 - 5295

88
[ 304858-65-9 ]
7-bromo-10-phenyl-2-(p-tolyl)-2-(trifluoromethyl)-2H-[1,3,5]oxadiazino[3,2-a]indole [ No CAS ]

Reference： [1]Organic Letters,2017,vol. 19,p. 5292 - 5295

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Ghs Precautionary Statements

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

Ghs Hazard Statements

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere