76088-98-7|7-Fluoroquinazoline-2,4(1H,3H)-dione| Ambeed

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Quality Control of [ 76088-98-7 ] Purity: 98% SDS Specification

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Product Details of [ 76088-98-7 ]

CAS No. :	76088-98-7
Formula :	C₈H₅FN₂O₂
M.W :	180.14
SMILES Code :	O=C(N1)NC2=C(C=CC(F)=C2)C1=O
MDL No. :	MFCD09954843
InChI Key :	TVXRSUFHSHBLOM-UHFFFAOYSA-N
Pubchem ID :	12666525

Safety of [ 76088-98-7 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 76088-98-7 ] Show Less

Physicochemical Properties

Num. heavy atoms	13
Num. arom. heavy atoms	10
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	3.0
Num. H-bond donors	2.0
Molar Refractivity	45.15
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	65.72 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.0
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	0.87
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.78
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.	1.03
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	2.62
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.26

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.07
Solubility	1.52 mg/ml ; 0.00843 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.	-1.83
Solubility	2.64 mg/ml ; 0.0147 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very 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	-3.42
Solubility	0.0683 mg/ml ; 0.000379 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.	-6.78 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	1.0
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	0.0 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)	1.84

Application In Synthesis of [ 76088-98-7 ]

* 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 [ 76088-98-7 ]

[ 76088-98-7 ] Synthesis Path-Downstream 1~26

2
[ 76088-98-7 ]
[ 1007308-74-8 ]

Yield	Reaction Conditions	Operation in experiment
66%	With sulfuric acid; potassium nitrate; at 0℃; for 1h;	Example 72, synthesis of the compound:; (8-allyl-N4-(3-chloro-4-methoxy-benzyl)-7-methoxy-N2,N2-dimethyI-6- nitro-quinazolin-2,4-diamine; Synthesis of the compound 16 in Reaction scheme 5; The compound 15 (4.29 g, 23.8 mmol) was added to H2SO4 (60 mL) and the mixture was cooled to 0C with stirring. KNO3 was added to the reaction mixture, followed by stirring at 0C for one hour. After completion of the reaction, the reaction mixture was poured into ice water with stirring and the resulting mixture was filtered under reduced pressure. The filtrate as a brown solid was added to MeOH. The resulting mixture was stirred for one hour and filtered to yield the compound 16 (3.55 g, 66%) as a brown solid.1H-NMR (DMSO-de) delta 11.81 (s, IH), 11.75 (s, IH), 8.55 (d, IH), 7.10(d, IH).

References: [1]Patent: WO2008/20711,2008,A1 .Location in patent: Page/Page column 26; 70.

3
[ 25057-77-6 ]
[ 76088-98-7 ]
[ 851013-56-4 ]

Yield	Reaction Conditions	Operation in experiment
58%		A solution of 7-fluoro-1H-quinazoline-2,4-dione (4.1 g, 23 mmol), dimethylpiperazine (6.2 mL, 46 mmol), and tripropylamine (8.7 mL, 46 mmol) in dioxane (55 mL), was cooled to 0 C. and treated with phosphorous oxychloride (6.4 mL, 68 mmol). The reaction mixture was heated to 100 C. for 1 h, cooled to ambient temperature and stirred an additional 16 h. Chloroform (about 200 mL) was added and the mixture was slowly poured over ice. After neutralizing to pH>10 with 25% NaOH (about 30 mL), the organic layer was separated. The aqueous layer was extracted again with chloroform, and the combined organic extracts were dried over sodium sulfate, filtered and concentrated. Silica gel chromatography (10% ethyl acetate in hexanes) afforded 3.7 g (58%) of the desired product as a light brown solid.

References: [1]Patent: US2005/96327,2005,A1 .Location in patent: Page/Page column 28.

4
[ 446-32-2 ]
[ 76088-98-7 ]

Yield	Reaction Conditions	Operation in experiment
71%		2-Amino-4-fluoro-benzoic acid (5.00 g, 32.2 mmol) in water (180 mL) and glacial acetic acid (3 mL) was warmed to 35 C. and slowly treated with a suspension of sodium cyanate (5.24 g, 80.6 mmol) in water (20 mL). Residual sodium cyanate was washed in with three additional portions of water (10 mL each). The reaction mixture was stirred an additional 30 min, after which sodium hydroxide (35 g, 880 mmol) was slowly added giving a white precipitate. Water (100 mL) was added, the reaction mixture was cooled to 0 C., and acidified to pH=4 with concentrated hydrochloric acid. The white solid was filtered, washed with water and dried in vacuo to afford 4.1 g (71%) of the desired product.
	With urea; In methanol;	a) A mixture of 0.2 g (1.3 mmol) of 2-amino-4-fluorobenzoic acid and 1.16 g of urea (20 mmol) was heated to 160 C. for 2 hrs. and at 180 C. for a further 2 hrs. The resulting brown mass was triturated with 200 ml of methanol, filtered off and dried in a vacuum. There were obtained: 167 mg (70%) of 7-fluoro-1,2,3,4-tetrahydroquinazoline-2,4-dione as yellow crystals; MS: me/e=180 (M+).

References: [1]Patent: US2005/96327,2005,A1 .Location in patent: Page/Page column 28.
[2]Patent: US5688803,1997,A .
[3]Chemical and Pharmaceutical Bulletin,2014,vol. 62,p. 824 - 829.

5
[ 446-32-2 ]
[ 57-13-6 ]
[ 76088-98-7 ]

Yield	Reaction Conditions	Operation in experiment
77%	at 220℃; for 1h;	A finely powdered mixtureof 4-fluoroanthranilic acid (24.0 g, 154.8 mmol) and urea (27.0 g, 450 mmol) was heated at220 C for 1 hour. During the heating a clear solution was obtained at190 C and solidified on continued heating. The mixture was cooled to25 C and water (500 ml) was added to it and boiled for 1 hour and cooled to25 C. The residue was filtered and dried to give the desired product (21.55 g, 77%). 1H NMR5 6. 88(m, 1 H), 6.91(m,1 H), 7.94(m,1 H).
56%	at 20 - 180℃; for 21.5h;Neat (no solvent);	EXAMPLE 21 7-(4-Amino-cvclohexylaminoV 1 H-quinazoline-2,4-dione; 21 A. 7-Fluoro- 1 H-quinazoline-2,4-dione; 2-Amino-4-fluoro benzoic acid (Ig, 6.45 mmol) and urea (5.96g, 99 mmol) were mixed together as solids and heated at 160 0C with stirring for 2 hours. The reaction mixture was then heated at 180 0C for a further 1.5 hours. The reaction mixture was allowed to cool to room temperature and stand for 18 hours. The hard solid residue was suspended in methanol and allowed to stand for 64 hours. The residue was triturated and filtered, washing with methanol. The product was suspended in 2N aqueous sodium hydroxide (100 ml) and heated with a hot air gun to give a fine suspension. The suspension was acidified to pH 1 with concentrated HCl causing a precipitate to form. The solid was filtered, washed with water and methanol and dried to yield the title compound as a beige solid (0.645g, 56% yield). LC/MS: (PS- P) Rt 2.18 [M-H]" 178.97.
	In neat (no solvent); at 150℃;	General procedure: 5.2.1.1 Quinazoline-2,4(1H,3H)-dione (2a) The mixture of 2-amino-benzoic acid (5 g, 36.46 mmol) and urea (50 g, 83.25 mmol) was stirred at 150 C for 7 h. The reaction mixture was cooled to 100 C and then water (50 mL) was added to quench the reaction. The crude product was obtained by filtration, then dissolved in NaOH aq (6 M, 500 mL). The pH was adjusted to 3 and a precipitate was formed. After filtration and dried under vacuum condition, compound 2a was obtained as white solid (4.5 g, 76.1%); 5.2.1.4 7-Fluoroquinazoline-2,4(1H,3H)-dione (2d) Following the preparation protocol of Section 5.2.1.1 , starting from 2-amino-4-fluorobenzoic acid (1.5 g, 9.67 mmol), the title compound 2d was obtained as yellow solid (1.13 g, 61.9%); mp 139-141 C; 1H NMR (300 MHz, DMSO-d6) delta (ppm): 11.35 (s, 1H), 11.26 (s, 1H), 7.95 (dd, J1 = 8.7 Hz, J2 = 6.6 Hz, 1H), 7.00-7.06 (m, 1H), 6.88-6.92 (m, 1H); HR-MS (ESI): m/z, Calcd for C8H6N2O2F [M+H]+ 181.0408, Found: 181.0404.

5.26 g

at 220℃; for 1h;

<Step 1> 7-fluoroquinazolin-2,4(1H,3H)-dione A mixture of 4-fluoroanthranilic acid (5 g, 32.2 mmol) and urea (5.8 g, 96.7 mmol) was stirred at 220 C. for 1 hour. After cooling the reaction solution, water was added thereto. The reaction solution was stirred at reflux for 1 hour, and stirred again at room temperature for 3 days. The resulting solid was filtered, washed with water and dried in vacuo to give the titled compound (5.26 g) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) delta 11.29 (brs, 2NH), 7.95 (t, 1H), 7.03 (t, 1H), 6.91 (d, 1H).

References: [1]Patent: WO2005/49033,2005,A1 .Location in patent: Page/Page column 112.
[2]Patent: WO2006/51290,2006,A2 .Location in patent: Page/Page column 117.
[3]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 681 - 693.
[4]Patent: US2016/90374,2016,A1 .Location in patent: Paragraph 0186; 0187.

6
[ 76088-98-7 ]
[ 174566-15-5 ]

Yield	Reaction Conditions	Operation in experiment
78%	With trichlorophosphate; for 72h;Heating / reflux;	A suspensionof 7-fluoro-2, 4-dioxo(1H, 3X) quinazoline (Method 98,1. 8 g, 10 mmol) inPOC13 (30 ml) was heated under reflux for 72 hours. The brown coloured solution was concentrated to dryness under vacuum. The residue was treated with ice water (50 ml) and filtered. The residue was washed with ice-cold water (10 ml) and dried to give the desired product(1. 7 g, 78%). 1H NMR(CDC13)5 7.92(m,1 H), 7.95 (d, J = 2.9 Hz, 1 H), 8.42(m,1 H). MS: m/z 219 (M+3), 217(M+1).
	In ice-water; trichlorophosphate;	b) 164 mg (0.9 mmol) of <strong>[76088-98-7]7-fluoro-1,2,3,4-tetrahydroquinazoline-2,4-dione</strong> were suspended in 3.5 ml (48 mmol) of phosphorus oxychloride and heated to 120 C. for 24 hrs. The reaction mixture was left to cool to room temperature and poured on to ice-water. The brown precipitate was filtered off under suction, dried and chromatographed over silica gel with methylene chloride as the eluent. 130 mg (67%) of 2,4-dichloro-7-fluoroquinazoline were obtained as orange coloured crystals; MS: me/e=216, 218 (M+).
3.82 g	With trichlorophosphate; for 72h;Reflux;	<Step 2> 2,4,-dichloro-7-fluoroquinazoline A mixture of 7-fluoroquinazoline-2,4(1H, 3H)-dione (5.26 g, 29.2 mmol) prepared in Step 1 and phosphorus oxychloride (85 ml) was stirred at reflux for 3 days. After cooling the reaction mixture to room temperature, the same was added into ice water. The resulting solid was filtered and dried in vacuo to give the titled compound (3.82 g) as a yellow solid. 1H NMR (400 MHz, CDCl3) delta 8.32 (m, 1H), 7.63 (d, 1H), 7.49 (t, 1H).

References: [1]Patent: WO2005/49033,2005,A1 .Location in patent: Page/Page column 113.
[2]Patent: US5688803,1997,A .
[3]Journal of Medicinal Chemistry,2011,vol. 54,p. 6028 - 6039.
[4]Patent: US2016/90374,2016,A1 .Location in patent: Paragraph 0188; 0189.
[5]Chemical and Pharmaceutical Bulletin,2014,vol. 62,p. 824 - 829.

7
[ 76088-98-7 ]
[ 425637-54-3 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6028 - 6039.

8
[ 76088-98-7 ]
C₁₀H₇ClFN₃O [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6028 - 6039.

9
[ 76088-98-7 ]
[ 425639-51-6 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6028 - 6039.

10
[ 590-28-3 ]
[ 446-32-2 ]
[ 76088-98-7 ]

Yield	Reaction Conditions	Operation in experiment
65%		Example 767-Fluoroquinazoline-2,4(lH,3H)-dioneTo a mixture of 2-amino-4-fluorobenzoic acid (4.0 g, 26 mmol) and potassium cyanate (3.5 g, 43 mmol) in water (200 mL) was added acetic acid (3 mL, 45 mmol) and the mixture was stirred at room temperature for about 5 h. To the mixture was added NaOH (15 g, 375 mmol) and it was stirred for another 1 h. The mixture was filtered and the solid was mixed in hot water, and it was adjusted to pH=5~6 by addition of acetic acid. The mixture was filtered and washed with water, dried to give the title compound (3.0 g, 65% yield) as gray solid. MS: m/z 181.1 [M+H]+
65%		To a mixture of 2-amino-4-fluorobenzoic acid (4.0 g, 26 mmol) and potassium cyanate (3.5 g, 43 mmol) in water (200 mL) was added acetic acid (3 mL, 45 mmol) and the mixture was stirred at room temperature for about 5 h. To the mixture was added NaOH (15 g, 375 mmol) and it was stirred for another 1 h. The mixture was filtered and the solid was mixed in hot water, and it was adjusted to pH=5?6 by addition of acetic acid. The mixture was filtered and washed with water, dried to give the title compound (3.0 g, 65% yield) as gray solid. MS: m/z 181.1 [M+H]+

References: [1]Patent: WO2012/130166,2012,A1 .Location in patent: Page/Page column 48.
[2]Patent: US2014/23642,2014,A1 .Location in patent: Paragraph 0411.

11
[ 999-97-3 ]
[ 76088-98-7 ]
C₁₄H₂₁FN₂O₂Si₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; In toluene;Reflux;	General procedure: 5.2.2.1 1-(3-Nitrobenzyl)quinazoline-2,4(1H,3H)-dione (5a) To a suspension of 2a (140 mg, 0.86 mmol) in toluene (4 mL) and hexamethyldisilazane (HMDS; 347 mg, 2.15 mmol), three drops of sulfuric acid were added with caution. The mixture was heated to reflux and stirred under refluxing for 8 h untill clear solution was obtained. After the removal of toluene and excess HMDS under vacuum distillation, 1-(bromomethyl)-3-nitrobenzene (744 mg, 3.44 mmol) was added to the residue. The reaction mixture was heated to 130 C and was stirred at this temperature for 3 h, the reaction mixture was diluted with 1,4-dioxane (2 mL) at 100 C, and then methanol (3 mL) was added at 70 C for 30 min. The suspension was cooled below 5 C and precipitates were collected by filtriation. After washing with methanol (5 mL) and water (5 mL), the crude product was dried under vacuum condition to afford 5a as white solid (200 mg, 77.3%);

References: [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 681 - 693.

12
[ 124-38-9 ]
[ 80517-22-2 ]
[ 76088-98-7 ]

References: [1]RSC Advances,2015,vol. 5,p. 5032 - 5037.

13
[ 76088-98-7 ]
[ 956101-10-3 ]

References: [1]Chemical and Pharmaceutical Bulletin,2014,vol. 62,p. 824 - 829.

14
4-fluoro-2-ureidobenzoic acid [ No CAS ]
[ 76088-98-7 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium hydroxide;	With 4-fluoro-2-aminobenzoic acid as raw material, we have explored the synthesis of quinazoline-2,4(1H,3H)-dione and the reaction conditions were optimized by HPLC-MS. The key to this synthesis is that in the first step of o-aminobenzoic acid with isocyanic acid as urea and in the second step urea is cyclized under alkaline conditions. The reaction solvent was first screened. Select the good solubility of acetonitrile as solvent, add 2. 0 times the equivalent of acetic acid for acidification of potassium isocyanate as Isocyanic acid and carried out at 50 C for 2 hours. LC-MS showed that the reaction solution contained 85% 4-fluoro-2-ureidobenzoic acid and 5% 65-fluoro-2-aminobenzoic acid which was not completely transformed. then reduce the reaction temperature to room temperature meanwhile extending the reaction time to 4 hours and 6 hours. LC-MS showed that after 6 hours, the starting material was completely converted to 4-fluoro-2-ureido benzoic acid with yield of 94%. Then, NaOH was added directly to the reaction solution. When 4 times the amount of base was added, LC-MS showed that the cyclization reaction was completed, and then the pH was adjusted to 1 by adding hydrochloric acid. The solvent was recovered under reduced pressure, separated by silica gel column chromatography to obtain 7-fluoroquinazoline-2, 4(1Eta, 3H)-dione with a yield of 91%. acetonitrile as solvent to obtain successful high yield quinazoline-2,4(1H,3H)-dione then we change the reaction solvent to water to also obtain efficient green target compound . At room temperature, the solubility of 4-fluoro-2-aminobenzoic acid in water is poor , When the temperature is raised to 80 C, 5g of raw materials can be dissolved in 100 ml of water,ater 2.0 times the equivalent of acetic acid acidification reaction solution, slowly dropping 1. 5 times the equivalent of potassium isocyanate aqueous solution then at 80 C reaction was continued for 6 hours and the reaction was complete. When the reaction temperature was lowered, the entire reaction solution was suspended, indicating that only a small amount of the raw material was dissolved in water. However, it was exciting to note that LC-MS showed that the reaction was still carried out after addition of 75% of Isocyanic acid. After 12 hours, the reaction was complete and the yield of compound 3a was 92% and with acetonitrile as solvent then there was no significant difference . The reaction was continued by slowly adding 4 times the equivalent alkali, after cyclization reaction is completed, adhust reaction solution PH 98%.And, when the raw material feeding amount increased to 1kg it can be possible to obtain same efficiency 7-fluoroquinazoline-2, 4(1Eta, 3H)-dione. With the water solvent, we successfully synthesized quinazolinodione at room temperature, 80 and when the reaction solvent is replaced with water, the entire synthesis process is simpler and requires no special purification to obtain a high purity target compound.

References: [1]Patent: CN105315217,2016,A .Location in patent: Paragraph 0018.
[2]Chemical and Pharmaceutical Bulletin,2014,vol. 62,p. 824 - 829.

15
C₈H₄FN₂O₂^(1-)*Na⁽¹⁺⁾ [ No CAS ]
[ 76088-98-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With hydrogenchloride; In water;pH < 1;Green chemistry; Large scale;	General procedure: pH of the reaction mixture was carefully adjusted to pH <1 with concentrated HCl, affording a white precipitate. After filtration and washing with water until pH 7 was attained, the desired products were obtained. The structures of the products were confirmed by spectral analyses, and the data agreed well with those reported in the literature. Characterization Data of Products 7-Fluoroquinazoline-2,4(1H,3H)-dione (2a): White solid, 1H-NMR (400 MHz, DMSO-d6) deltaH: 11.34, 11.24 (each 1H, s), 7.95 (1H, dd, J1=11.2 Hz, J2=8.8 Hz), 7.01 (1H, m), 6.88 (1H, dd, J1=8.8 Hz, J2=2.8 Hz) ppm; 13C-NMR (100 MHz, DMSO-d6) deltaC: 165.7 (d, J=332 Hz), 161.9, 150.2, 142.8 (d, J=16 Hz), 130.1 (d, J=16 Hz), 113.2 (d, J=2 Hz), 110.2 (d, J=32 Hz), 101.4 (d, J=35 Hz) ppm. High resolution-electrospray ionization (HR-ESI)-MS: Calcd for C8H6FN2O2, 181.0413, Found 181.0418 [M+H]+.

References: [1]Chemical and Pharmaceutical Bulletin,2014,vol. 62,p. 824 - 829.

16
methyl (4-fluoro-2-nitrobenzoyl)carbamate [ No CAS ]
[ 76088-98-7 ]

Yield	Reaction Conditions	Operation in experiment
90.3%	With palladium 10% on activated carbon; p-toluenesulfonic acid monohydrate; hydrogen; In methanol; at 20℃; for 3h;	General procedure: To a magnetically stirred solution of 2a (200 mg, 0.892 mmol) in CH3OH (50 mL) was added 10% Pd/C (10% Pd loaded on Carbon wetted with ca. 55% water, 20 mg) and PTSA · H2O (8.6 mg, 0.045 mmol). The reaction mixture was stirred under an atmosphere of hydrogen at room temperature for 3 h. After filtration of Pd/C and concentration under reduced pressure at 45 C, 20 mL H2O was added to the residue and the mixture was stirred at 0 C for 1 h.

References: [1]Synthetic Communications,2018,vol. 48,p. 1183 - 1189.

17
[ 76088-98-7 ]
C₁₉H₁₆Cl₂N₄O₄ [ No CAS ]