1-(4-Amino-3-fluorophenyl)ethanone

(R)-N-(4-{1 -[3-(4-tert-Butyl-benzyl)-ureido]-ethyl}-2-fluoro-6-vinyl- phenyl)-methanesulfonamide; Step i: 1-(4-Amino-3-fluorophenyl)ethanoneA 25 ml two neck round-bottom flask was filled with Ar gas and the solution of 2-fluoro-4-iodophenylamine (1500mg, 6.33mmol) in DMF, palladium ( II ) acetate (0.19mmol, 42.62mg), 1 , 3-bisdiphenyl phosphinopropane (0.06eq, 0.38mmol, 156.65mg), Thallium( I )acetate (6.96mmol, 1834.19mg), butyl vinyl ether(2eq, 12.66mmol, 1.64ml) were put into the flask. The reaction mixture was heated and stirred for 15hr. The reaction mixture was poured into the THF soulution, and then 10percent HCI was added slowly. The reaction mixture was extracted with ethyl acetate (300*3), EPO A 25 ml of two neck round-bottom flask was filled with argon gas and the solution of 2-Fluoro-4-iodophenylamine (1500mg, 6.33mmol) in DMF, Palladium(Π) acetate (0.19mmol, 42.62mg), 1, 3-bisdiphenyl phosphinopropane(0.06eq, 0.38mmol, 156.65mg), Thallium( l )acetate (6.96mmol, 1834.19mg), and Butyl vinyl ether(2eq, 12.66mmol, 1.64ml) were put into the flask. The reaction mixture was heated and stirred for 15hrs. The reaction mixture was poured into the THF solution, and then 10percent HCl was added slowly. The reaction mixture was extracted with ethyl acetate(300.x.3), washed with HReference 2-[(4-acetyl-2-fluorophenyl)amino]-6-[bis(4-methoxybenzyl)amino]-9-(propan-2-yl)-7, 9-dihydro-8H-purin-8-one The compound prepared in Reference (3 g), 1-(4-amino-3-fluorophenyl) ethanone (1.1 g) and a solution of cesium carbonate (6.3 g) in dimethoxyethane (21 mL) / tert-butanol) was degassed and was purged with argon. To this reaction mixture, 2-(dicyclohexylphosphino)-2', 4', 6'-triisopropylbiphenyl (310 mg) and tris (dibenzylideneacetone) dipalladium (0) (290 mg) was added. The reaction mixture was stirred at 90 C for 4 hours. Further, 2-(dicyclohexylphosphino)-2', 4', 6'-triisopropylbiphenyl (155 mg) and tris (dibenzylideneacetone) dipalladium (0) (145 mg) were added. The reaction mixture was stirred at 90 C for 4 hours. The reaction mixture was filtered through Celite (trade name). Celite was washed with ethyl acetate. The obtained filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained crude product was washed with MTBE, and was filtrated. The filtrate was dried to give the title compound (2.4 g) having the following physical properties. TLC: Rf 0.28 (hexane : ethyl acetate = 3 : 2); 1H-NMR (CDCl3): delta1.54-1.61, 2.54, 3.81, 4.60-4.78, 6.86-6.93, 7.16-7.26, 7.56-7.61, 7.65-7.71, 8.48-8.56.All reactions werecarried out according to the procedure written below unless otherwise noted. The starting anilines (0.1 mmol) in dryCH2Cl2 (2.5 mL) was treated with carboxylic acid (1.3 mmol)and NaBH(OAc)3 (1.6 mmol) at room temperature overnight.Saturated aqueous NaHCO3 was dropped into the reactionmixture, and then the mixture was stirred until the foaming stopped. After extracting with EtOAc, the organic layerwas dried over MgSO4. Removal of solvent from EtOAcextract under reduced pressure by a rotary evaporator gavecrude products that were purified by column chromatography. The obtained products, 4-chloro-N, N-diethylaniline (2), )N-ethylindoline (7), ) 1-(4-ethylaminophenyl) ethanone (9), )4-ethylaminobenzophenone (14), ) and N-(4-chlorophenyl)-5-methyl-2-pyrrolidone (18)) were confirmed by the previously reported spectroscopic data. 1-(4-Ethylamino-3-fluorophenyl)ethanone (12) Pale yel-low oil, 1H-NMR (500 MHz, CDCl3) delta: 1.32 (3H, t, J=7.4 Hz), 2.50 (3H, s), 3.27 (1H, dq, J=5.7, 7.4 Hz), 4.37 (1H, br s), 6.64(1H, dd, J=8.1, 8.6 Hz), 7.59 (1H, dd, J=2.3, 12.6 Hz), 7.67(1H, dd, J=2.3, 8.6 Hz). 13C-NMR (125 MHz, CDCl3) delta: 14.5, 26.0, 37.6, 109.7 (d), 114.0 (d), 126.8, 141.2 (d), 149.4, 151.3, 195.7. IR (KBr) cm-1: 3438, 1666, 1611, 1537. Electrosprayionization-time-of-flight (ESI-TOF)-MS m/z: 182.0977 (Calcdfor C10H13FNO: 182.0976). MS m/z: 182 ([M+H]+).Step 2: 1-(4-Amino-3-fluoro-5-iodophenyl)ethanone; (0.30mmol, 45.6mg) was added in the acetonitrile, and then NIS (0.33mol, 73.73mg) was added. A reaction mixture was stirred for 12 hrs. A reaction mixture was quenched by sodium thiosulfate. A reaction mixture was extracted with EtOAC and H2O, a combined organic layer was washed with brine and dried over Na2SO4 and then concentrated in vacuo. The remain layer was purified with column chormactography (n-Hexane: EtOAc = 7 : 1) to yield a brownish solid (53.92mg, 64.43%). Mp: 124~126 C; IR (KBr pellet): 3455, 3331, 3073, 2921, 1659, 1259 cm-1; 1H NMR(400MHz, CDCl3) : delta 8.01 (dd, 1 H, J =1.6, 1.2Hz), 7.65(dd, 1H, J =11.6, 2.0Hz), 4.61(bs, 2H), 2.46(s, 3H).(R)-N-(4-{1 -[3-(4-tert-Butyl-benzyl)-ureido]-ethyl}-2-fluoro-6-vinyl- phenyl)-methanesulfonamide; Step i: A 25 ml of two neck round-bottom flask was filled with argon gas and the solution of 2-Fluoro-4-iodophenylamine (1500mg, 6.33mmol) in DMF, Palladium(Pi) acetate (0.19mmol, 42.62mg), 1, 3-bisdiphenyl phosphinopropane(0.06eq, 0.38mmol, 156.65mg), Thallium( l )acetate (6.96mmol, 1834.19mg), and Butyl vinyl ether(2eq, 12.66mmol, 1.64ml) were put into the flask. The reaction mixture was heated and stirred for 15hrs. The reaction mixture was poured into the THF solution, and then 10% HCl was added slowly. The reaction mixture was extracted with ethyl acetate(300×3), washed with H2O, and brine. The combined organic solution was dried over Na2SO4 and then purified with column chromatography (n-Hx: EA= 3: 1) to yield a pale yellow solid (343.0mg, 35.40%). Mp:77~79C; IR(KBr pellet, cm-1): 3373, 3326, 1663, 1296; 1H NMR(400MHz, CDCl3): delta 7.53(?, 2H), 6.69(?, 1H), 3.41(s, 2H), 2.43(s, 3H).To a solution of

Molecular Weight:153.15
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:153.058992041
Monoisotopic Mass:153.058992041
Topological Polar Surface Area:43.1
Heavy Atom Count:11
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes