55496-69-0|4-Chloro-7-methoxy-6-nitroquinazoline| Ambeed

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Quality Control of [ 55496-69-0 ] Purity: 95% SDS Specification

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Product Details of [ 55496-69-0 ]

CAS No. :	55496-69-0
Formula :	C₉H₆ClN₃O₃
M.W :	239.62
SMILES Code :	COC1=C(C=C2C(Cl)=NC=NC2=C1)[N+]([O-])=O
MDL No. :	MFCD11869864
InChI Key :	MJFJWOAETHEGGW-UHFFFAOYSA-N
Pubchem ID :	10490187

Safety of [ 55496-69-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H320-H335
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338

Computational Chemistry of [ 55496-69-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	16
Num. arom. heavy atoms	10
Fraction Csp3	0.11
Num. rotatable bonds	2
Num. H-bond acceptors	5.0
Num. H-bond donors	0.0
Molar Refractivity	59.86
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	80.83 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.63
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.3
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.2
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	0.53
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	0.36
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.41

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.11
Solubility	0.188 mg/ml ; 0.000785 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.64
Solubility	0.0555 mg/ml ; 0.000232 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.46
Solubility	0.0833 mg/ml ; 0.000348 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.13 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	2.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.04

Application In Synthesis of [ 55496-69-0 ]

* 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.

Downstream synthetic route of [ 55496-69-0 ]

[ 55496-69-0 ] Synthesis Path-Downstream 1~36

1
[ 591-19-5 ]
[ 55496-69-0 ]
[ 171745-10-1 ]

References: [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 267 - 276.

2
[ 1012057-47-4 ]
[ 55496-69-0 ]

Yield	Reaction Conditions	Operation in experiment
83%	With trichlorophosphate; for 4h;Heating / reflux;	Compound 0304 (3.8 g, 17.2 mmol) was suspended in POCI3 (75 mL), the mixture was heated to reflux for 4 hours. The additional POCI3 was removed in a vacuum. The residue was dissolved in a mixture of dichloromethane (50 mL) and aqueous NaHCCh (50 mL) .The organic layer was dried and the solvent was removed to give the title compound 0305 (3.4 g, 83%). 1H NMR (DMSO-J6): delta 4.05 (s, 3H), 7.44 (s, IH), 8.27 (s, IH), 8.53 (s, IH).
83%	With trichlorophosphate; for 4h;Heating / reflux;	Step 22d. 4-Chloro-7-methoxy-6-nitroquinazoline (compound 0305) Compound 0304 (3.8 g, 17.2 mmol) was suspended in POCl3 (75 mL), the mixture was heated to reflux for 4 hours. The additional POCl3 was removed in a vacuum. The residue was dissolved in a mixture of dichloromethane (50 mL) and aqueous NaHCO3 (50 mL). The organic layer was dried and the solvent was removed to give the title compound 0305 (3.4 g, 83%). 1H NMR (DMSO-d6): delta 4.05 (s, 3H), 7.44 (s, 1H), 8.27 (s, 1H), 8.53 (s, 1H).
83%		Step 22d. 4-Chloro-7-methoxy-6-nitroquinazoline (compound 0305); Compound 0304 (3.8 g, 17.2 mmol) was suspended in POCl3 (75 mL), the mixture was heated to reflux for 4 hours. The additional POCl3 was removed in a vacuum. The residue was dissolved in a mixture of dichloromethane (50 mL) and aqueous NaHCO3 (50 mL). The organic layer was dried and the solvent was removed to give the title compound 0305 (3.4 g, 83%). 1H NMR (DMSO-d6): delta 4.05 (s, 3H), 7.44 (s, 1H), 8.27 (s, 1H), 8.53 (s, 1H).

	With thionyl chloride; In N,N-dimethyl-formamide; for 4h;Reflux;	DMF (0.5 mL) was added to a solution of 7-Methoxy-6-nitroquinazolin-4(3H)-one (1-g, 1.23 g, 5.56 mmol) in SOCl2 (8 mL) and the mixture was heated to reflux for 4 h. The volatiles were removed under reduced pressure to give (1-h, 1.2 g, 5.0 mmol).
		[054] DMF (0.5 mL) was added to a solution of 7-methoxy-6-nitroquinazolin-4(3H)-one (1-g, 1.23 g, 5.56 mmol) in SOCl2 (8 mL) and the mixture was heated to reflux for 4 h. The volatiles were removed under reduced pressure to give (1-h, 1.2 g, 5.0 mmol).
	With thionyl chloride; In N,N-dimethyl-formamide; for 2h;Reflux;	A solution of 6-nitro-7-methoxy-3H-quinazolin-4-one (4.42 g, 20.0 mmol)Then 0.4 mL of DMF was added and the mixture was stirred at reflux for 2 h.The solution gradually turned brown,The reaction was stopped, cooled to room temperature,The excess S0C12 was distilled off,To give 4-chloro-6-nitro-7-methoxyquinazoline as a pale yellow solid. The resulting pale yellow solid was crushed and addedInto 30 mL of petroleum ether, the petroleum ether was distilled off under reduced pressure. The procedure was repeated twice with petroleum ether to remove the residual S0C12 to obtain a yellow solid.The yellow solid was transferred to a three-necked flask without purification and aniline (2.05 g, 22.0 mmol), isopropanol 170 mL, refluxStirred for 2 h, cooled to room temperature, the solid collected, washed with isopropanol, dried, yellow solid 6-nitro-7-methoxy-4-anilineYl) quinazoline in a yield of 61.9%.

References: [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 267 - 276.
[2]Patent: WO2008/33747,2008,A2 .Location in patent: Page/Page column 130.
[3]Patent: US2009/76022,2009,A1 .Location in patent: Page/Page column 74-75.
[4]Journal of Medicinal Chemistry,2010,vol. 53,p. 2000 - 2009.
[5]Patent: US2009/111772,2009,A1 .Location in patent: Page/Page column 73.
[6]Patent: WO2012/182,2012,A1 .Location in patent: Page/Page column 12.
[7]Patent: WO2012/356,2012,A1 .Location in patent: Page/Page column 12.
[8]Bulletin of the Korean Chemical Society,2015,vol. 36,p. 1933 - 1935.
[9]Journal of Medicinal Chemistry,2016,vol. 59,p. 8103 - 8124.
[10]Patent: CN103382182,2016,B .Location in patent: Paragraph 0272; 0273; 0280; 0281.

3
[ 367-21-5 ]
[ 55496-69-0 ]
[ 1012057-48-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	In isopropyl alcohol; for 3h;Heating / reflux;	A mixture of compound 0305 (3.4 g, 14,2 mmol) and 3-chloro-4-fluroaniline (0406) (2.2 g, 15.2 mmol) and isopropanol (120 mL) was stirred at reflux for 3 hours. The mixture was cooled to ambient temperature and the precipitate was isolated, washed with methanol and ether and then dried to give the title compound 0307 (4.66 g, 85%). 1H NMR (DMSO-J6): .£4.10 (s, 3H), 7.55 (dd, 2H ), 7.74 (m, IH), 8.07 (dd, IH), 8.90 (s, IH), 9.55 (s, IH), 11.6 (s, IH).
85%	In isopropyl alcohol; for 3h;Heating / reflux;	Step 22e. N-(3-chloro-4-fluorophenyl)-7-methoxy-6-nitroquinazolin-4-amine Hydrochloride (compound 0307) A mixture of compound 0305 (3.4 g, 14.2 mmol) and 3-chloro-4-fluoroaniline (0406) (2.2 g, 15.2 mmol) and isopropanol (120 mL) was stirred at reflux for 3 hours. The mixture was cooled to ambient temperature and the precipitate was isolated, washed with methanol and ether and then dried to give the title compound 0307 (4.66 g, 85%). 1H NMR (DMSO-d6): delta4.10 (s, 3H), 7.55 (dd, 2H), 7.74 (m, 1H), 8.07 (dd, 1H), 8.90 (s, 1H), 9.55 (s, 1H), 11.6 (s, 1H).
85%	In isopropyl alcohol; for 3h;Heating / reflux;	Step 22e. N-(3-chloro-4-fluorophenyl)-7-methoxy-6-nitroquinazolin-4-amine Hydrochloride (compound 0307); A mixture of compound 0305 (3.4 g, 14.2 mmol) and 3-chloro-4-fluoroaniline (0406) (2.2 g, 15.2 mmol) and isopropanol (120 mL) was stirred at reflux for 3 hours. The mixture was cooled to ambient temperature and the precipitate was isolated, washed with methanol and ether and then dried to give the title compound 0307 (4.66 g, 85%). 1H NMR (DMSO-d6): delta4.10 (s, 3H), 7.55 (dd, 2H), 7.74 (m, 1H), 8.07 (dd, 1H), 8.90 (s, 1H), 9.55 (s, 1H), 11.6 (s, 1H).

References: [1]Patent: WO2008/33747,2008,A2 .Location in patent: Page/Page column 130.
[2]Patent: US2009/76022,2009,A1 .Location in patent: Page/Page column 75.
[3]Journal of Medicinal Chemistry,2010,vol. 53,p. 2000 - 2009.
[4]Patent: US2009/111772,2009,A1 .Location in patent: Page/Page column 73.

4
[ 55496-69-0 ]
N⁴-(3-bromophenyl)-7-methoxyquinazoline-4,6-diamine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 267 - 276.

5
[ 53449-14-2 ]
[ 55496-69-0 ]

References: [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 267 - 276.
[2]Patent: CN103382182,2016,B .
[3]Patent: US2009/111772,2009,A1 .

6
[ 5638-76-6 ]
[ 55496-69-0 ]
[ 55496-70-3 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In ethanol; sodium hydrogencarbonate;	EXAMPLE VIII 6-Amino-7-methoxy-4-(N-methyl-2-[2-pyridyl]ethylamino)quinazoline A mixture of <strong>[55496-69-0]4-chloro-7-methoxy-6-nitroquinazoline</strong> (19.0 g), 2-(2-[N-methylamino]ethyl)pyridine (11.25 g), triethylamine (17 g) and ethanol (300 ml) was refluxed for 1 1/2 hours and the reaction mixture evaporated in vacuo to dryness. The residue was triturated in aqueous sodium bicarbonate solution and the yellow solid formed was subsequently extracted into chloroform. Evaporation of the dried organic solution afforded a solid which was recrystallized three times from ethyl acetate giving 10.1 g of 7-methoxy-6-nitro-4-(N-methyl-2-[2-pyridyl]ethylamino)quinazoline.

References: [1]Patent: US3971783,1976,A .

7
[ 16499-57-3 ]
[ 55496-69-0 ]

References: [1]Patent: WO2012/182,2012,A1 .
[2]Patent: WO2012/356,2012,A1 .

8
[ 446-32-2 ]
[ 55496-69-0 ]

References: [1]Patent: WO2012/182,2012,A1 .
[2]Patent: WO2012/356,2012,A1 .

9
[ 162012-69-3 ]
[ 55496-69-0 ]

References: [1]Patent: WO2012/182,2012,A1 .
[2]Patent: WO2012/356,2012,A1 .
[3]Bulletin of the Korean Chemical Society,2015,vol. 36,p. 1933 - 1935.
[4]Journal of Medicinal Chemistry,2016,vol. 59,p. 8103 - 8124.

10
[ 55496-69-0 ]
[ 202197-31-7 ]
[ 1353644-75-3 ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane; for 3h;Reflux;	A mixture of <strong>[55496-69-0]4-chloro-7-methoxy-6-nitroquinazoline</strong> (1-h, 1.2g, 5.02mmol) and l-(3-fluorobenzyl)-lH-indazol-5-amine (1-c, 1.2g, 4.98mmol) in dioxane (40mL) was heated to reflux for 3 h. It was then cooled to the ambient temperature. The precipitates were obtained by filtration and purified by chromatography on silica gel to give 1-i (1.7 g, 3.88 mmol) as yellow solid.
	In 1,4-dioxane; for 3h;Reflux;	[055] A mixture of <strong>[55496-69-0]4-chloro-7-methoxy-6-nitroquinazoline</strong> (1-h, 1.2 g, 5.02 mmol) and l-(3-fluorobenzyl)-lH-indazol-5-amine (1-c, 1.2 g, 4.98 mmol) in dioxane (40 mL) was heated to reflux for 3 h. It was then cooled to the ambient temperature. The precipitates were obtained by filtration and purified by chromatography on silica gel to give 1-i (1.7 g, 3.88 mmol) as a yellow solid.

References: [1]Patent: WO2012/182,2012,A1 .Location in patent: Page/Page column 12.
[2]Patent: WO2012/356,2012,A1 .Location in patent: Page/Page column 12.

11
[ 55496-69-0 ]
[ 897025-61-5 ]

References: [1]Patent: WO2012/182,2012,A1 .
[2]Patent: WO2012/356,2012,A1 .

12
[ 55496-69-0 ]
[ 1353644-76-4 ]

References: [1]Patent: WO2012/182,2012,A1 .
[2]Patent: WO2012/356,2012,A1 .

13
[ 55496-69-0 ]
[ 1353644-68-4 ]

References: [1]Patent: WO2012/182,2012,A1 .
[2]Patent: WO2012/356,2012,A1 .

15
[ 55496-69-0 ]
[ 1363151-24-9 ]

References: [1]Patent: WO2015/6492,2015,A1 .

16
[ 55496-69-0 ]
tert-butyl 2-((7-methoxy-4-(methylamino)quinazolin-6-yl)carbamoyl)pyrrolidine-1-carboxylate [ No CAS ]

References: [1]Patent: WO2015/6492,2015,A1 .

17
[ 55496-69-0 ]
(S)-tert-butyl 2-((4-(3-benzyl-1-methylureido)-7-methoxyquinazolin-6-yl)carbamoyl)pyrrolidine-1-carboxylate [ No CAS ]

References: [1]Patent: WO2015/6492,2015,A1 .

18
[ 55496-69-0 ]
(S)-N-(4-(3-benzyl-1-methylureido)-7-methoxyquinazolin-6-yl)pyrrolidine-2-carboxamide [ No CAS ]

References: [1]Patent: WO2015/6492,2015,A1 .

19
[ 55496-69-0 ]
(S)-1-acryloyl-N-(4-(3-benzyl-1-methylureido)-7-methoxyquinazolin-6-yl)pyrrolidine-2-carboxamide [ No CAS ]

References: [1]Patent: WO2015/6492,2015,A1 .

20
[ 74-89-5 ]
[ 55496-69-0 ]
[ 1363151-22-7 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; at 0 - 20℃; for 4h;	To a solution of 4ch1oro-?7rnethoxy--6nitroquinazoiine (1 .() g, 4.1 mrnoi) in anhydrous THF (10 niL) was added 2.0 M methylarnine solution in THF (4.4 inL) at 0 C. The reaction mixture was stirred for 4 hours at room temperature and concentrated to half of the original vohime of solvent under reduced pressure. To the reaction mixture was added water (100 mL) and the resulting precipitate was collected by filtration. The solid was blowndry using nitrogen gas to give 7-inethoxy-N-inethyl-6-nitroquinazolim4-aniine (870 mg, 89% yield) as a bright yellow solid.

References: [1]Patent: WO2015/6492,2015,A1 .Location in patent: Page/Page column 77; 78.

21
[ 55496-69-0 ]
[ 897384-05-3 ]

References: [1]Bulletin of the Korean Chemical Society,2015,vol. 36,p. 1933 - 1935.

22
[ 55496-69-0 ]
N<SUP>4</SUP>-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-7-methoxyquinazoline-4,6-diamine [ No CAS ]

References: [1]Bulletin of the Korean Chemical Society,2015,vol. 36,p. 1933 - 1935.

23
[ 55496-69-0 ]
(2S)-2-{4-[3-chloro-4-(pyridin-2-ylmethoxy)-phenylamino]-7-methoxy-quinazolin-6-ylcarbamoyl}-pyrrolidine-1-carboxylic acid t-butylester [ No CAS ]

References: [1]Bulletin of the Korean Chemical Society,2015,vol. 36,p. 1933 - 1935.

24
[ 55496-69-0 ]
[ 524955-09-7 ]
[ 897384-03-1 ]

Yield	Reaction Conditions	Operation in experiment
92%	In isopropyl alcohol; at 60℃; for 3h;	Step 3: N-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-7-methoxy-6-nitroquinazoline-4-amine The 3-chloro-4-(pyridin-2-ylmethoxy)aniline(3.5 g, 14 mmol), <strong>[55496-69-0]4-chloro-7-methoxy-6-nitroquinazoline</strong> (3.4 g, 14 mmol) were added into isopropanol (40 mL), stirred at 60 C. for 3 h. Then the solution was filtered; the filter cake was washed with isopropanol, dried, and the compound shown in the title (5.6 g, 92%) was obtained. 1H NMR (DMSO-d6): delta 10.91 (1H, br), 9.34 (1H, s), 8.80 (1H, s), 8.63 (1H, d, J=4.4 Hz), 7.97-7.91 (2H, m), 7.68-7.61 (2H, m), 7.50 (1H, s), 7.44-7.40 (1H, m), 7.34 (1H, d, J=9.2 Hz), 5.34 (2H, s), 4.09 (3H, s).

References: [1]Patent: US2016/214964,2016,A1 .Location in patent: Paragraph 0142.
[2]Bulletin of the Korean Chemical Society,2015,vol. 36,p. 1933 - 1935.

25
[ 1194097-41-0 ]
[ 55496-69-0 ]

References: [1]Bulletin of the Korean Chemical Society,2015,vol. 36,p. 1933 - 1935.

26
[ 55496-69-0 ]
4-hydroxy-N-(pyridine-2-yl)benzamide [ No CAS ]
4-[(7-methoxy-6-nitroquinazolin-4-yl)oxy]-N-(pyridin-2-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	With potassium carbonate; In acetonitrile; at 150℃; for 1h;Microwave irradiation;	A solution of <strong>[55496-69-0]4-chloro-7-methoxy-6-nitroquinazoline</strong> (201 mg, 0.84 mmol) in acetonitrile (15 mL) was added to a mixture of 4-hydroxy-N-(pyridin-2-yl)benzamide (215 mg, 1.01 mmol, 1.2 eq.) and K2CO3(174 mg, 1.26 mmol, 1.5 eq.) and the suspension was heated in the microwave for 1 hour at 150 C. The reaction mixture was diluted with water, filtered and washed water. The solids were coevaporated twice with toluene to give 162 mg of 4-[(7-methoxy-6- nitroquinazolin-4-yl)oxy]-N-(pyridin-2-yl)benzamide (46%) as an off white solid. LC-MS (Method A) Rt: 7.28 mm; m/z 418.1 (M+H)+.

References: [1]Patent: WO2016/55982,2016,A1 .Location in patent: Paragraph 00196.

27
[ 55496-69-0 ]
[ 202197-26-0 ]
N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-7-methoxy-6-nitroquinazolin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	In isopropyl alcohol; at 60℃; for 3h;	Step 3: N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-7-methoxy-6-nitroquinazoline-4-amine The 3-chloro-4-(3-fluorobenzyloxy)-aniline (2.82 g, 11.1 mmol), <strong>[55496-69-0]4-chloro-7-methoxy-6-nitroquinazoline</strong> (2.68 g, 11.2 mmol) were added into isopropanol (30 mL), stirred at 60 C. for 3 h. Then the solution was filtered, washed with isopropanol and dried, and the compound shown in the title (4.8 g, 95%) was obtained. 1H NMR (DMSO-d6): delta 10.94 (1H, br), 9.33 (1H, s), 8.79 (1H, s), 7.91 (1H, d, J=2.4 Hz), 7.64-7.61 (1H, m), 7.47-7.40 (2H, m), 7.31-7.27 (3H, m), 7.18-7.13 (1H, m), 5.25 (2H, s), 4.06 (3H, s).

References: [1]Patent: US2016/214964,2016,A1 .Location in patent: Paragraph 0128.

28
[ 54060-30-9 ]
[ 55496-69-0 ]
(3-ethynylphenyl)-(7-methoxy-6-nitroquinazolin-4-yl)amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	In isopropyl alcohol; for 1h;Reflux;	Step 1: N-(3-ethynylphenyl)-7-methoxy-6-nitroquinazoline-4-amine The <strong>[55496-69-0]4-chloro-7-methoxy-6-nitroquinazoline</strong> (1.00 g, 4.17 mmol) was added into a solution of 3-ethynylaniline (0.49 g, 4.17 mmol) in isopropanol (15 mL), refluxed with heating for 1 h. Once the reaction was complete, the solution was cooled and filtered, and the compound shown in the title (1.12 g, 84%) was obtained. 1H NMR (DMSO-d6): delta 11.08 (1H, br), 9.47 (1H, s), 8.89 (1H, s), 7.95 (1H, s), 7.79-7.82 (1H, m), 7.56 (1H, s), 7.47-7.52 (1H, m), 7.37-7.40 (1H, m), 4.27 (1H, s), 4.10 (3H, s).

References: [1]Patent: US2016/214964,2016,A1 .Location in patent: Paragraph 0155.

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[ 54060-30-9 ]
[ 55496-69-0 ]
[ 1012057-52-1 ]