[ CAS No. 194423-15-9 ] {[proInfo.proName]}

Name: 194423-15-9|N-(4-((3-Bromophenyl)amino)quinazolin-6-yl)acrylamide|99+%
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Quality Control of [ 194423-15-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 194423-15-9 ]

Product Details of [ 194423-15-9 ]

CAS No. :	194423-15-9	MDL No. :	MFCD02179207
Formula :	C₁₇H₁₃BrN₄O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HTUBKQUPEREOGA-UHFFFAOYSA-N
M.W :	369.22	Pubchem ID :	4708
Synonyms :

Calculated chemistry of [ 194423-15-9 ]

Physicochemical Properties

Num. heavy atoms :	23
Num. arom. heavy atoms :	16
Fraction Csp3 :	0.0
Num. rotatable bonds :	5
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	95.43
TPSA :	66.91 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-5.8 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.53
Log Po/w (XLOGP3) :	3.87
Log Po/w (WLOGP) :	4.07
Log Po/w (MLOGP) :	3.05
Log Po/w (SILICOS-IT) :	3.28
Consensus Log Po/w :	3.36

Druglikeness

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

Water Solubility

Log S (ESOL) :	-4.75
Solubility :	0.00654 mg/ml ; 0.0000177 mol/l
Class :	Moderately soluble
Log S (Ali) :	-4.97
Solubility :	0.00394 mg/ml ; 0.0000107 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-7.14
Solubility :	0.0000266 mg/ml ; 0.0000000721 mol/l
Class :	Poorly soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	2.6

Safety of [ 194423-15-9 ]

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 [ 194423-15-9 ]

* 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 [ 194423-15-9 ]
Downstream synthetic route of [ 194423-15-9 ]

[ 194423-15-9 ] Synthesis Path-Upstream 1~8

1
[ 79-10-7 ]
[ 169205-78-1 ]
[ 194423-15-9 ]

Yield	Reaction Conditions	Operation in experiment
45%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 4.25 h;	To a solution of 6-amino-4-[(3-bromophenyl)amino]quinazoline (2.0 g, 6.35 mmol) in dry DMF (20 ML) under N2 was added acrylic acid (12.7 mmol, 0.87 mL). The resulting solution was cooled to 0° C. and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI.HCl) (7.62 mmol, 1.46 g) was added. The reaction was stirred at 0° C. for 15 minutes and then allowed to warm to room temperature and stirred for a further 2 hours, after which additional acrylic acid (0.30 mL) and EDCI.HCl (0.30 g) were added. After a further 2 hours, the reaction was complete by tlc, solvent was removed under reduced pressure, and the resulting residue diluted with saturated NaHCO3 and repeatedly extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Column chromatography on grade III alumina eluding with EtOAc/MeOH (95:5) followed by recrystallization from EtOAc/hexane gave a spongy white solid, which upon several hours under high vacuum gave N-[4-[(3-bromophenyl)amino]quinazolin-6-yl]acrylamide (1.06 g, 45percent) as a cream powder, mp 258-261° C. 1H NMR [(CD3)2SO, 200 MHz]: δ 10.51 (s, 1H, CONH), 9.93 (s, 1H, NH), 8.83 (br s, 1H, H-5), 8.59 (s, 1H, H-2), 8.18 (br s, 1H, H-2'), 7.94-7.78 (m, 3H, H-6', 8, 5'), 7.40-7.27 (m, 2H, H-7, 4'), 6.54 (dd, J =9.8 Hz, J =17.0 Hz, 1H, CH2CHCO), 6.36 (dd, J =2.1 Hz, J =16.9 Hz, 1H, CH2CHCO), 5.85 (dd, J =2.0 Hz, J =9.7 Hz, 1H, CE2CHCO). Mass spectrum (CI): 371 (95, 81BrMH+), 370 (53, 81BrM+), 369 (100, 79BrMH+), 368 (33, 79BrM+). Analysis calculated for C17H13BrN4O requires: C, 55.30; H, 3.55; N, 15.17percent. Found: C, 55.19; H, 3.34; N, 14.88percent.

Reference： [1] Journal of Medicinal Chemistry, 1999, vol. 42, # 10, p. 1803 - 1815
[2] Patent: US6344459, 2002, B1, . Location in patent: Page column 48

2
[ 256409-20-8 ]
[ 194423-15-9 ]

Yield	Reaction Conditions	Operation in experiment
83.4%	With potassium <i>tert</i>-butylate In DMF (N,N-dimethyl-formamide) at 20℃; for 5 h;	EXAMPLE 3 4-(3-bromo phenyl amine)-6-(vinyl amide) quinazoline (II) from (7, X=O) To a solution of 4-(3-bromo phenyl amine)-6-(3-methoxy propionyl amide) quinazoline (7, X=O) (0.201 g, 0.5 mmol) in dimethyl formamide (2.5 mL), was added potassium tert-butoxide (0.178 g, 1.5 mmol). The mixture was stirred at ambient temperature for five hours, preferably overnight, until the reaction was completed (TLC/HPLC). A darkening and a small exotherm (34 °C) observed initially upon the base addition. The mixture was partition between ethyl acetate (10 mL) and aqueous sodium chloride (10 mL, 20percent). The layers were separated and the organic layer extracted to neutrality with aqueous sodium chloride (3x10 mL, 20percent), dried over anhydrous magnesium sulfate (1.5 g) for at least one hour, and the slurry filtered over a plug of silica gel (3 g). The silica gel plug was washed with a solution of ethyl acetate-10percent methanol (20 mL-2 mL), and the combined filtrates concentrated under vacuum to a yellow solid (0.200 g). Ethyl ether (5 mL) was added and the mixture stirred for one hour, filtered, and the solid washed with ethyl ether (2x0.5 mL) and dried under vacuum (60 °C) to provide the title compound as a light yellow solid, 0.154 g (83.4percent); m.p. 288-290 °C(dec.). TLC (dichloromethane-5percent methanol) showed one single spot at R_f 0.40, identical to authentic; ¹H NMR (300 MHz, DMSO-d₆) 5.85 (d, J_cis=11Hz, 1H, C=CH geminal vinyl), 6.35 (d, J_trans=15Hz, 1H, C=CH geminal vinyl), 6.54 (q, J_trans=10Hz, J_cis=7Hz, 1H, C=CH-C=O- vicinal vinyl), 7.20-8.90 (m, 8H, Ar-H), 9.94 (s, 1H, NH amide), 10.55 (s, 1H, NH amine).

Reference： [1] Patent: EP1100788, 2005, B1, . Location in patent: Page/Page column 7

3
[ 256409-24-2 ]
[ 194423-15-9 ]

Yield	Reaction Conditions	Operation in experiment
55%	With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 1 h;	EXAMPLE 11 4-(3-bromo phenyl amine)-6-(vinyl amide) quinazoline (II) from (12) To a solution of 4-(3-bromo phenyl amine)-6-(3-methylsulfoxido propionyl amide) quinazoline (12) (0.043g, 0.1 mmol) in DMF (2 mL), was added potassiumtert-butoxide (0.035 g, 0.3 mmol). The reaction mixture was stirred at ambient temperature for one hour, whereupon the reaction was completed (TLC/HPLC). A darkening, but no exotherm was observed initially upon the base addition. The reaction mixture was partitioned between ethyl acetate (10 mL) and aqueous sodium chloride (10 mL, 20percent). The layers were separated, the organic layer extracted to neutrality with aqueous sodium chloride (3x10 mL, 20percent), dried over anhydrous magnesium sulfate (1.5 g) for at least one hour, and filtered over a plug of silica gel (3 g). The plug was washed with a solution of ethyl acetate-10percent methanol (20 mL-2 mL). The filtrates were concentrated under vacuum to a yellow solid (0.025 g). Ethyl ether (3 mL) was added, the mixture stirred for one hour, filtered, washed with ethyl ether (3x0.5 mL) and dried it under vacuum (60 °C). The resulting light yellow solid, 0.020 g (55.0percent) was identical to the title compound (II); m.p. 288-290 °C(dec.).

Reference： [1] Patent: EP1100788, 2005, B1, . Location in patent: Page/Page column 9-10

4
[ 814-68-6 ]
[ 169205-78-1 ]
[ 194423-15-9 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 7, p. 3482 - 3488
[2] Journal of Medicinal Chemistry, 2010, vol. 53, # 7, p. 2892 - 2901
[3] Journal of Medicinal Chemistry, 2001, vol. 44, # 17, p. 2719 - 2734

5
[ 256409-22-0 ]
[ 194423-15-9 ]

Yield	Reaction Conditions	Operation in experiment
50.5%	With potassium <i>tert</i>-butylate In DMF (N,N-dimethyl-formamide) at 20℃; for 48 h;	EXAMPLE 6 4-(3-bromo phenyl amine)-6-(vinyl amide) quinazoline (II) from (7; X=S) To a solution of 4-(3-bromo phenyl amine)-6-(3-methylthio propionyl amide) quinazoline (7, X=S) (0.208g, 0.5 mmol) in dimethyl formamide (2.5 mL), was added potassium tert-butoxide (0.178 g, 1.5 mmol) and the mixture was stirred at ambient temperature. A darkening and a small exotherm (34 °C) was observed initially upon the base addition. The reaction was progressing slowly at ambient temperature and it was not completed (TLC/HPLC) after two days. The reaction mixture was partitioned between ethyl acetate (10 mL)/aqueous sodium chloride (10 mL, 20percent). The layers were separated and the organic layer was extracted to neutrality with aqueous sodium chloride (3x10 mL, 20percent). The organic layer was dried over anhydrous magnesium sulfate (1.5 g) for at least one hour and filtered over a plug of silica gel (3 g). The silica plug was washed with a solution of ethyl acetate-10percent methanol (20 mL-2 mL). The filtrate was concentrated under vacuum to a yellow solid (0.184 g) and added to ethyl ether (5 mL). The mixture was stirred for one hour, filtered; the solid was washed with ethyl ether (2x0.5 mL) and dried under vacuum (60 °C). The light yellow solid, 0.150 g (81.2percent) was a mixture of 50.5percent the title compound (II) and 38.0percent starting material (7, X=S) by HPLC. This was confirmed by TLC (dichloromethane-5percent methanol) which showed two spots in a 50/40 ratio of (1)/(11) respectively. The ¹H NMR (300 MHz, DMSO-d₆) indicated the same ratio 5/4 of the characteristic frequencies of both compounds (II) and (7) respectively.

Reference： [1] Patent: EP1100788, 2005, B1, . Location in patent: Page/Page column 8

6
[ 169205-78-1 ]
[ 194423-15-9 ]

Reference： [1] Patent: US6323209, 2001, B1,
[2] Patent: US5760041, 1998, A,
[3] Patent: US5929080, 1999, A,
[4] Patent: EP787722, 1997, A1,
[5] Patent: EP980244, 2003, B1,

7
[ 17420-30-3 ]
[ 194423-15-9 ]

Reference： [1] Journal of Medicinal Chemistry, 2001, vol. 44, # 17, p. 2719 - 2734

8
[ 169205-77-0 ]
[ 194423-15-9 ]

Reference： [1] Journal of Medicinal Chemistry, 2001, vol. 44, # 17, p. 2719 - 2734

[ 194423-15-9 ] Synthesis Path-Downstream 1~18

1
[ 79-10-7 ]
[ 169205-78-1 ]
[ 194423-15-9 ]

Yield	Reaction Conditions	Operation in experiment
45%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 0 - 20℃; for 4.25h;	To a solution of 6-amino-4-[(3-bromophenyl)amino]quinazoline (2.0 g, 6.35 mmol) in dry DMF (20 ML) under N2 was added acrylic acid (12.7 mmol, 0.87 mL). The resulting solution was cooled to 0 C. and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI.HCl) (7.62 mmol, 1.46 g) was added. The reaction was stirred at 0 C. for 15 minutes and then allowed to warm to room temperature and stirred for a further 2 hours, after which additional acrylic acid (0.30 mL) and EDCI.HCl (0.30 g) were added. After a further 2 hours, the reaction was complete by tlc, solvent was removed under reduced pressure, and the resulting residue diluted with saturated NaHCO3 and repeatedly extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Column chromatography on grade III alumina eluding with EtOAc/MeOH (95:5) followed by recrystallization from EtOAc/hexane gave a spongy white solid, which upon several hours under high vacuum gave N-[4-[(3-bromophenyl)amino]quinazolin-6-yl]acrylamide (1.06 g, 45%) as a cream powder, mp 258-261 C. 1H NMR [(CD3)2SO, 200 MHz]: delta 10.51 (s, 1H, CONH), 9.93 (s, 1H, NH), 8.83 (br s, 1H, H-5), 8.59 (s, 1H, H-2), 8.18 (br s, 1H, H-2'), 7.94-7.78 (m, 3H, H-6', 8, 5'), 7.40-7.27 (m, 2H, H-7, 4'), 6.54 (dd, J =9.8 Hz, J =17.0 Hz, 1H, CH2CHCO), 6.36 (dd, J =2.1 Hz, J =16.9 Hz, 1H, CH2CHCO), 5.85 (dd, J =2.0 Hz, J =9.7 Hz, 1H, CE2CHCO). Mass spectrum (CI): 371 (95, 81BrMH+), 370 (53, 81BrM+), 369 (100, 79BrMH+), 368 (33, 79BrM+). Analysis calculated for C17H13BrN4O requires: C, 55.30; H, 3.55; N, 15.17%. Found: C, 55.19; H, 3.34; N, 14.88%.

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 1803 - 1815
[2]Patent: US6344459,2002,B1 .Location in patent: Page column 48

2
[ 110-91-8 ]
[ 194423-15-9 ]
[ 198961-88-5 ]

Yield	Reaction Conditions	Operation in experiment
78%	toluene-4-sulfonic acid; In tetrahydrofuran; at 50℃; for 4.0h;Heating / reflux;	A stirred solution of N-[4-[(3-bromophenyl)amino]quinazolin-6-yl]acrylamide (1.78 g, 4.82 mmol), morpholine (excess, 4.0 mL) and p-toluenesulfonic acid (catalytic) in THF (50 mL) was heated at 50 C. for 4 hours before being concentrated under reduced pressure, diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, concentrated under reduced pressure, and chromatographed on silica gel eluting with MeOH/CH2Cl2/EtOAc (15:40:45) to give N-[4-[(3-bromophenyl)amino]quinazolin-6-yl]-3-morpholino-propylamide (1.86 g, 78%) as a cream powder, mp (EtOAc) 184-186 C. 1H NMR [(CD3)2SO]: delta 10.37 (s, 1H, CONH), 9.91 (s, 1H, NH), 8.72 (d, J=1.9 Hz, 1H, H-5), 8.58 (s, 1H, H-2), 8.17 (t, J=2.1 Hz, 1H, H-2'), 7.86 (m, 2H, H-7, 6'), 7.78 (d, J=8.9 Hz, 1H, H-8), 7.35 (t, J=8.0 Hz, 1H, H-5'), 7.29 (dt, Jt=1.2 Hz, Jd=8.0 Hz, 1H, H-4'), 3.40 (t, J=4.6 Hz, 4H, morpholino methylene), 2.69 (t, J=6.6 Hz, 2H, NCH2CH2CONH), 2.58 (t, J=6.6 Hz, 2H, NCH2CH2CONH), 2.44 (br s, 4H, morpholino methylene). 13C NMR: delta 170.24, 157.18, 152.86, 146.48, 141.13, 136.87, 130.21, 128.39, 127.01, 125.74, 124.21, 121.03, 120.79, 115.40, 111.46, 66.09 (2), 54.04, 53.00 (2), 33.66. Analysis calculated for C21H22BrN52 requires: C, 55.3; H, 4.9; N, 15.3%. Found: C, 55.1; H, 5.2; N, 15.2%.

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 429 - 440
[2]Patent: US6344459,2002,B1 .Location in patent: Page column 60-61

3
[ 814-68-6 ]
[ 169205-78-1 ]
[ 194423-15-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 3482 - 3488
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 2892 - 2901
[3]Journal of Medicinal Chemistry,2001,vol. 44,p. 2719 - 2734

4
[ 17420-30-3 ]
[ 194423-15-9 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 2719 - 2734

5
[ 169205-77-0 ]
[ 194423-15-9 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 2719 - 2734

6
(E)-N'-(2-cyano-4-nitrophenyl)-N,N-dimethylimidoformamide [ No CAS ]
[ 194423-15-9 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 2719 - 2734

7
[ 194423-15-9 ]
[ 198961-89-6 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 429 - 440

8
[ 194423-15-9 ]
N-[4-[(3-bromophenyl)-amino]-quinazolin-6-yl]-N-[3-morpholinopropyl]-acrylamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 429 - 440

9
[ 256409-22-0 ]
[ 194423-15-9 ]

Yield	Reaction Conditions	Operation in experiment
50.5%	With potassium tert-butylate; In DMF (N,N-dimethyl-formamide); at 20℃; for 48.0h;Product distribution / selectivity;	EXAMPLE 6 4-(3-bromo phenyl amine)-6-(vinyl amide) quinazoline (II) from (7; X=S) To a solution of 4-(3-bromo phenyl amine)-6-(3-methylthio propionyl amide) quinazoline (7, X=S) (0.208g, 0.5 mmol) in dimethyl formamide (2.5 mL), was added potassium tert-butoxide (0.178 g, 1.5 mmol) and the mixture was stirred at ambient temperature. A darkening and a small exotherm (34 C) was observed initially upon the base addition. The reaction was progressing slowly at ambient temperature and it was not completed (TLC/HPLC) after two days. The reaction mixture was partitioned between ethyl acetate (10 mL)/aqueous sodium chloride (10 mL, 20%). The layers were separated and the organic layer was extracted to neutrality with aqueous sodium chloride (3x10 mL, 20%). The organic layer was dried over anhydrous magnesium sulfate (1.5 g) for at least one hour and filtered over a plug of silica gel (3 g). The silica plug was washed with a solution of ethyl acetate-10% methanol (20 mL-2 mL). The filtrate was concentrated under vacuum to a yellow solid (0.184 g) and added to ethyl ether (5 mL). The mixture was stirred for one hour, filtered; the solid was washed with ethyl ether (2x0.5 mL) and dried under vacuum (60 C). The light yellow solid, 0.150 g (81.2%) was a mixture of 50.5% the title compound (II) and 38.0% starting material (7, X=S) by HPLC. This was confirmed by TLC (dichloromethane-5% methanol) which showed two spots in a 50/40 ratio of (1)/(11) respectively. The 1H NMR (300 MHz, DMSO-d6) indicated the same ratio 5/4 of the characteristic frequencies of both compounds (II) and (7) respectively.

Reference： [1]Patent: EP1100788,2005,B1 .Location in patent: Page/Page column 8

10
[ 256409-20-8 ]
[ 194423-15-9 ]

Yield	Reaction Conditions	Operation in experiment
83.4%	With potassium tert-butylate; In DMF (N,N-dimethyl-formamide); at 20℃; for 5.0h;Product distribution / selectivity;	EXAMPLE 3 4-(3-bromo phenyl amine)-6-(vinyl amide) quinazoline (II) from (7, X=O) To a solution of 4-(3-bromo phenyl amine)-6-(3-methoxy propionyl amide) quinazoline (7, X=O) (0.201 g, 0.5 mmol) in dimethyl formamide (2.5 mL), was added potassium tert-butoxide (0.178 g, 1.5 mmol). The mixture was stirred at ambient temperature for five hours, preferably overnight, until the reaction was completed (TLC/HPLC). A darkening and a small exotherm (34 C) observed initially upon the base addition. The mixture was partition between ethyl acetate (10 mL) and aqueous sodium chloride (10 mL, 20%). The layers were separated and the organic layer extracted to neutrality with aqueous sodium chloride (3x10 mL, 20%), dried over anhydrous magnesium sulfate (1.5 g) for at least one hour, and the slurry filtered over a plug of silica gel (3 g). The silica gel plug was washed with a solution of ethyl acetate-10% methanol (20 mL-2 mL), and the combined filtrates concentrated under vacuum to a yellow solid (0.200 g). Ethyl ether (5 mL) was added and the mixture stirred for one hour, filtered, and the solid washed with ethyl ether (2x0.5 mL) and dried under vacuum (60 C) to provide the title compound as a light yellow solid, 0.154 g (83.4%); m.p. 288-290 C(dec.). TLC (dichloromethane-5% methanol) showed one single spot at Rf 0.40, identical to authentic; 1H NMR (300 MHz, DMSO-d6) 5.85 (d, Jcis=11Hz, 1H, C=CH geminal vinyl), 6.35 (d, Jtrans=15Hz, 1H, C=CH geminal vinyl), 6.54 (q, Jtrans=10Hz, Jcis=7Hz, 1H, C=CH-C=O- vicinal vinyl), 7.20-8.90 (m, 8H, Ar-H), 9.94 (s, 1H, NH amide), 10.55 (s, 1H, NH amine).

Reference： [1]Patent: EP1100788,2005,B1 .Location in patent: Page/Page column 7

11
[ 256409-24-2 ]
[ 194423-15-9 ]

Yield	Reaction Conditions	Operation in experiment
55.0%	With potassium tert-butylate; In N,N-dimethyl-formamide; at 20℃; for 1.0h;Product distribution / selectivity;	EXAMPLE 11 4-(3-bromo phenyl amine)-6-(vinyl amide) quinazoline (II) from (12) To a solution of 4-(3-bromo phenyl amine)-6-(3-methylsulfoxido propionyl amide) quinazoline (12) (0.043g, 0.1 mmol) in DMF (2 mL), was added potassiumtert-butoxide (0.035 g, 0.3 mmol). The reaction mixture was stirred at ambient temperature for one hour, whereupon the reaction was completed (TLC/HPLC). A darkening, but no exotherm was observed initially upon the base addition. The reaction mixture was partitioned between ethyl acetate (10 mL) and aqueous sodium chloride (10 mL, 20%). The layers were separated, the organic layer extracted to neutrality with aqueous sodium chloride (3x10 mL, 20%), dried over anhydrous magnesium sulfate (1.5 g) for at least one hour, and filtered over a plug of silica gel (3 g). The plug was washed with a solution of ethyl acetate-10% methanol (20 mL-2 mL). The filtrates were concentrated under vacuum to a yellow solid (0.025 g). Ethyl ether (3 mL) was added, the mixture stirred for one hour, filtered, washed with ethyl ether (3x0.5 mL) and dried it under vacuum (60 C). The resulting light yellow solid, 0.020 g (55.0%) was identical to the title compound (II); m.p. 288-290 C(dec.).

Reference： [1]Patent: EP1100788,2005,B1 .Location in patent: Page/Page column 9-10

12
4-(3-bromophenylamine)-6-(3-methylsulfonopropionylamide)-quinazoline [ No CAS ]
[ 194423-15-9 ]

Yield	Reaction Conditions	Operation in experiment
74.3%	With potassium tert-butylate; In DMF (N,N-dimethyl-formamide); at 20 - 24℃; for 2.0h;Product distribution / selectivity;	EXAMPLE 12 4-(3-bromo phenyl amine)-6-(vinyl amide) quinazoline (II), from (13) To a solution of 4-(3-bromo phenyl amine)-6-(3-methylsulfono propionyl amide) quinazoline (13) (0.090g, 0.1 mmol) in DMF (1.5 mL), was added potassium tert-butoxide (0.035 g, 0.3 mmol). The reaction mixture was stirred at ambient temperature for 2 hours, whereupon the reaction was completed (TLC/HPLC). A darkening and a slight exotherm (22 to 24 C) was observed initially upon the base addition. The mixture was partitioned between ethyl acetate (10 mL) and aqueous sodium chloride (10 mL, 20%). The layers were separated; the organic layer extracted to neutrality with aqueous sodium chloride (3x10 mL, 20%), dried over anhydrous magnesium sulfate (1.5 g) for at least one hour and filtered over a plug of silica gel (3 g). The plug was washed with a solution of ethyl acetate-10% methanol (20 mL-2 mL). The combined filtrates were concentrated under vacuum to a yellow solid (0.075 g) which was added to it ethyl ether (3 mL), stirred for one hour, filtered, washed with ethyl ether (3x0.5 mL) and dried under vacuum (60 C). The light yellow solid, 0.055 g (74.3%) was identical to the title compound (1); m.p. 288-290 C(dec.). TLC (dichloromethane-5% methanol) showed one single spot at Rf 0.40, identical to authentic; 1H NMR (300 MHz, DMSO-d6) 5.85 (d, Jcis=11Hz, 1H, C=CH geminal vinyl), 6.35 (d, Jtrans=15Hz, 1H, C=CH geminal vinyl), 6.54 (q, Jtrans=10Hz, Jcis=7Hz, 1H, C=CH-C=O- vicinal vinyl), 7.20-8.90 (m, 8H, Ar-H), 9.94 (s, 1H, NH amide), 10.55 (s, 1H, NH amine).

Reference： [1]Patent: EP1100788,2005,B1 .Location in patent: Page/Page column 10

13
[ 169205-78-1 ]
[ 194423-15-9 ]

Yield	Reaction Conditions	Operation in experiment
	In pyridine;	EXAMPLE 13 N-[4-[(3-Bromophenyl)amino]-6-quinazolinyl]-2-propenamide A solution of 2.0 g of N-(3-bromophenyl)-4,6-quinazolindiamine in 10 ml of pyridine was cooled in an ice bath and a solution of 0.61 ml of acryoyl chloride in 30 ml of ether was added dropwise at 0 C. After stirring at room temperature for 3.5 hours, the solvents were removed at reduced pressure. The residue was purified by chromatography to give 0.2 g of N-[4-[(3-bromophenyl)amino]-6-quinazolinyl]-2-propenamide: mass spectrum (m/e): M+H 369.
	In pyridine;	Example 13 N-[4-[(3-Bromophenyl)amino]-6-quinazolinyl]-2-propenamide A solution of 2.0 g of N-(3-bromophenyl)-4,6-quinazolindiamine in 10 ml of pyridine was cooled in an ice bath and a solution of 0.61 ml of acryoyl chloride in 30 ml of ether was added dropwise at 0C. After stirring at room temperature for 3.5 hours, the solvents were removed at reduced pressure. The residue was purified by chromatography to give 0.2 g of N-[4-[(3-bromophenyl)amino]-6-quinazolinyl]-2-propenamide: mass spectrum (m/e): M+H 369.

Reference： [1]Patent: US6323209,2001,B1
[2]Patent: EP787722,1997,A1

15
[ 70-18-8 ]
[ 194423-15-9 ]
C₁₀H₁₇N₃O₆S*C₁₇H₁₃BrN₄O [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 2038 - 2050

16
[ 70-18-8 ]
[ 194423-15-9 ]
C₂₇H₃₀BrN₇O₇S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 2251 - 2264

17
[ 60-23-1 ]
[ 194423-15-9 ]
C₁₉H₂₀BrN₅OS [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 2251 - 2264

18
[ CAS Unavailable ]
[ 194423-15-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: acetic acid 2: ethanol; acetic acid 3: pyridine

Reference： [1]Current Patent Assignee: PFIZER INC - US5760041, 1998, A Current Patent Assignee: PFIZER INC - US5929080, 1999, A Current Patent Assignee: PFIZER INC - EP787722, 1997, A1 Current Patent Assignee: PFIZER INC - EP980244, 2003, B1 Current Patent Assignee: PFIZER INC - US6323209, 2001, B1

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H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 194423-15-9 ] {[proInfo.proName]}

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[ 194423-15-9 ] Synthesis Path-Upstream 1~8

[ 194423-15-9 ] Synthesis Path-Downstream 1~18

Related Functional Groups of [ 194423-15-9 ]

Aryls

Alkenes

Bromides

Amides

Amines

Related Parent Nucleus of [ 194423-15-9 ]

Quinazolines

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[ 194423-15-9 ]

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[ 194423-15-9 ]