2-FLUOROACRYLICACID

In a 250 ml four-necked flask, 2-fluoropropenal (8.89 g, 0.12 mol)m-cpba 26 g (0.15 mol), Dichloromethane 30g, incubated at 20 stirring 2h, cooled to about 0 , Filtration, the filtrate was concentrated to dryness to give crude 2-fluoroacrylic acid, Crystallization with 10g n-heptane to obtain 2-fluoro acrylic acid products.Yield 92percent.8.98 g (71.87 mmol) of 1-bromo-1-fluoroethene, 8.01 g (79.2 mmol) of triethylamine, 51.5 mg (0.072 mmol) of dichloro[bis(diphenylphosphinophenyl)ether]palladium (II), and 36 mE of non-dried methanol were placed in a 1 50-mE stainless autoclave, and 1.0 MPaG carbon monoxide was introduced thereto, followed by stirring at 100° C. for 13 hours. After completion of the reaction, the autoclave was cooled, and the unreacted gas was purged. The autoclave was opened, and 186 mg (1.0 mmol) of hexafluorobenzenewas added as an internal standard substance, followed by stirring. The mixture was then allowed to stand for a short period of time to precipitate the salt. The supernatant was diluted with deuterated chloroform, and subjected to quantification based on 19F-NMR integral values. The diluted supernatant was found to contain 50.93 mmol (yield: 70.9percent) of 2-fluoroacrylic acid methyl ester, 10.13 mmol (yield:14.1percent) of 2-fluoroacrylic acid, and 8.12 mmol (recovery:11.3percent) of unreacted 1 -bromo-1 -fluoroethene. The conversion was 87.5percent, and the selectivity was 81.0percent.General procedure: Oxalyl dichloride (1.56 mmol, 0.14 mL) was added to the solution of the tested acid (1.72 mmol) in CH2Cl2 (5 mL) and DMF (a drop, about 0.05 mL) at 0 C under Ar atmosphere within 10 min. After the solution was stirred for 3 h at the room temperature, a solution of 3a-i (1.32 mmol) in dichloromethane (8.0 mL) was added at 0 C. The reaction solution was then warmed to room temperature and stirred for overnight. After quenched with saturated NaHCO3 aqueous solution, the mixture was extracted with EtOAc (2×15 mL), and the combined organic layers were washed with brine (20 mL) and dried over NaSO4. After filtration and concentration, the residue was purified by column chromatography to give the acylated product with two rotamers, and the isolated yields were shown in Table 2. (2.Oeq.) (54 mg) was dissolved in DCM (10 ml)3 drops of DMF were added, Under ice-cooling conditions, Oxalyl chloride (1.7 eq.) (44 [mu] v)In the ice bath conditions for 30min, Remove the ice bath, Natural recovery to room temperature, The reaction was carried out for 2 hours, (4-fluorophenylamino) -6-amino-7- (tetrahydrofuran-3-oxy) quinazoline(1 eq.) (112 mg) was dissolved in DCM (20 ml)Stir at 0 C for 5 min, Was added to the above acid chloride solution, Et3N (4 Oeq.) (169yL) was added, In the ice bath conditions for 30min, Remove the ice bath, After natural recovery to room temperature, The reaction was stirred overnight.After completion of the reaction, Concentrated to dry under reduced pressure crude, Purification by column chromatography (mobile phase 10: lDCM / MeOH) afforded N- (4- (3-chloro-4-fluorophenylamino) -7- (tetrahydrofuran-3-oxy) quinazoline- Yl) -2-fluorobut-2-enamide 80mgGeneral procedure: We used indole 7 as starting material to synthesize interediates15a-c by the method reported in the literature [32]. Different substituted acrylic acids were chlorinated by POCl3 to obtain the corresponding acyl chloride at 80 C. Under an ice bath, differently substituted acryl chloride was dissolved in dichloromethane and stirred at 0 C for 10-30 min. Another intermediates 15a-c were added to the above acryl chloride solution, and then added NaHCO3 solid powder, stirred at 0 C for 0.5-3 h. After the reaction was completed, the reaction mixture was filtered and solvent was distilled off under reduced pressure. The crude product was purified using flash chromatography with dichloromethane/methanol(v/v, from 50:1 to 20:1) as eluentsAdd in a 50mL eggplant bottle

Molecular Weight:90.05
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:90.01170750
Monoisotopic Mass:90.01170750
Topological Polar Surface Area:37.3
Heavy Atom Count:6
Complexity:86.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes