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CAS No. : | 446-32-2 |
Formula : | C7H6FNO2 |
M.W : | 155.13 |
SMILES Code : | O=C(O)C1=CC=C(F)C=C1N |
MDL No. : | MFCD00075553 |
InChI Key : | LGPVTNAJFDUWLF-UHFFFAOYSA-N |
Pubchem ID : | 2724967 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With thionyl chloride In ethanol | A. Synthesis of ethyl 2-amino-4-fluorobenzoate To a chilled solution of 2-amino-4-fluorobenzoic acid (1.57 g, 10.1 mmol) in absolute ethanol (20 mL) was added neat thionyl chloride (4.4 mL, 60 mmol). The reaction mixture was refluxed for 4 days total, with addition of more SOCl2 (8 mL, 110 mmol), then concentrated, diluted with EtOAc, washed with 2N NaOH, dried and concentrated in vacuo to give ethyl 2-amino-4-fluorobenzoate (1.73 g, 94percent). |
94% | With thionyl chloride In ethanol | A. Synthesis of ethyl 2-amino-4-fluorobenzoate To a chilled solution of 2-amino-4-fluorobenzoic acid (1.57 g, 10.1 mmol) in absolute ethanol (20 mL) was added neat thionyl chloride (4.4 mL, 60 mmol). The reaction mixture was refluxed for 4 days total, with addition of more SOCl2 (8 mL, 110 mmol), then concentrated, diluted with EtOAc, washed with 2N NaOH, dried and concentrated in vacuo to give ethyl 2-amino-4-fluorobenzoate (1.73 g, 94percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | for 96 h; Reflux | A. Synthesis of ethyl 2-amino-4-fluorobenzoate (0244) To a chilled solution of 2-amino-4-fluorobenzoic acid (1.57 g, 10.1 mmol) in absolute ethanol (20 mL) was added neat thionyl chloride (4.4 mL, 60 mmol). The reaction mixture was refluxed for 4 days total, with addition of more SOCl2 (8 mL, 110 mmol), then concentrated, diluted with EtOAc, washed with 2N NaOH, dried and concentrated in vacuo to give ethyl 2-amino-4-fluorobenzoate (1.73 g, 94percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | To a 0 C. mixture of 2-amino-4-fluorobenzoic acid (1.18 g, 7.6 mmol) in 12N hydrochloric acid (2.3 mL) and water (13.7 mL) was added dropwise a solution of sodium nitrite (543 mg, 7.9 mmol) in water (1.2 mL). This resulting diazonium salt solution was stirred 10 min at 0 C. A solution of potassium iodide (1.9 g) in sulfuric acid (450 35 muL) and water (3.2 mL) was added dropwise to the 0 C. solution. The reaction mixture was heated to 100 C. for 2 h then cooled to room temperature. 10% sodium bisulfite solution was added and stirred. The precipitate was filtered, washed with water, air dried and recrystallized from toluene. [00389] mp 144-6 C. MS(m/e): 265(M-1). [00390] Analysis for C7H4FIO2: [00391] Calcd: C, 31.61; H, 1.52, N, 0; I, 47.71; Found: C, 31.93; H, 2.14; N, 0.14; I, 42.75. |
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+). |
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). |
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]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With iodine; sodium hydrogencarbonate; sodium sulfate; In acetonitrile; at 20℃; for 5h; | General procedure: To a stirred mixture of 1aA (0.42 g, 2.0 mmol) and 2a (0.279 g, 2.0 mmol) in MeCN (15 mL) were added NaHCO3 (0.252 g, 3.0 mmol), I2 (0.762 g, 3.0 mmol) and anhydrous Na2SO4 (0.289 g, 2.0 mmol) at room temperature. The reaction was allowed to proceed at room temperature until complete consumption of starting material as monitored by TLC (ca. 5 h). After the reaction was complete, the mixture was washed with saturated Na2S2O3 solution, extracted with EtOAc (2×25 mL), dried over anhydrous Na2SO4, and evaporated in vacuum on a rotary evaporator to afford a residue. This residue was purified by column chromatography on silica gel using hexanes-EtOAc (70:30, v/v) as the eluent to furnish 0.85 g (94%) of 3aAa as a white solid. 4.2.2 4-Fluoro-17-iodo-18-phenyl-9-oxa-1-azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-one (3aAb) Yield: 84% (0.78 g from 0.42 g) as a gray solid, mp: 156-158 C; Rf=0.68 (CH2Cl2-MeOH, 9.5:0.5, v/v); IR (KBr) ν: 1726, 1292, 788 cm-1. 1H NMR (300 MHz, CDCl3): δ (ppm)=6.15 (d, 1H, J=8.7 Hz, ArH), 6.87 (d, 1H, J=8.1 Hz, ArH), 7.11 (s, 2H, CH), 7.26-7.61 (m, 7H, ArH), 7.76 (d, 1H, J=7.2 Hz, ArH), 8.06 (s, 1H, ArH); 13C NMR (75 MHz, CDCl3): δ (ppm)=90.6, 100.8, 103.9, 112.4 (d, J=25.5 Hz), 114.5 (d, J=22.5 Hz), 123.3, 125.6(2C), 128.7, 129.2, 130.2, 131.6, 132.8, 134.5, 134.9, 142.9, 145.6, 151.7, 153.2, 153.5158.5, 162.9. MS (ESI+): m/z=470.0. ESI-HRMS calculated for C22H13FINO2 [MH]+: 470.0053, found: 470.0034. |
Tags: 2-Amino-4-fluorobenzoic acid | Fluorinated Building Blocks | Carboxylic Acids | Amines | Aryls | Organic Building Blocks | 446-32-2
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