7-Bromo-2,3-dihydro-1H-inden-1-one

To a stirring solution of compound 3 (1.0 g, 6.8 mmol) in 48percent HBraq (2 mL) and EtOH (8 mL) was added NaNO2 (0.62 g, 8.6 mmol) dissolved in H20 (1 mL) at 0 °C and kept at 0 °C for 15 mm. Then a solution of CuBr (0.54 g, 3.6 mmol) in 48percent HBraq (8 mL) was added to the mixture at95 °C and kept at 95 °C for 15 mm. After consumption of the starting material (by TLC), the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with saturated NaHCO3 aq. Combined organic extracts were dried over anhydrous Na2504 and concentrated under reduced pressure to obtain crude product, which was purified by silica gel column chromatography eluting with 10percent EtOAc /PE to afford compound 4 (0.54 g, 37percent) as an off-white solid. LC-MS: m/z = 212.0 [M+H]In the case of Aluminum chloride (7.40 g, 55.6 mmol) and sodium chloride (2.15 g, 37.1 mmol) were added to a 100 ml flask and heated to 130 ° C., then 2-bromophenyl-2-chloroethyl ketone (4.60 g , 18.5 mmol) was slowly added, The mixture was stirred at 160 ° C. for 1 hour. After the reaction, it was cooled to 30 ° C. and quenched with ice water. ThickAfter adjustment to pH = 5 with hydrochloric acid, the organic phase and aqueous phase were separated and the aqueous phase was extracted with 100 ml of dichloromethane, And the organic phase was collected and washed with 100 ml of water and 100 ml of saturated brine, And the solvent was distilled off under reduced pressure to obtain a crude product. Further, a silica gel column (Petroleum ether / ethyl acetate = 30/1) to obtain 1.60 g (yield 33percent) of 7-bromo-1-indanone.In a 1000 ml round bottom flask, 47.8 g of o-bromoacetophenone (compound-I-b) was dissolved inIn N, N-dimethylacetamide (600 ml), 6.5 g of ferric chloride hexahydrate was subsequently added.And 129.7 g of potassium persulfate, heated to 100 ° C, At the same time, air is continuously blown into the reaction liquid by an air pump, and the mixture is stirred at this temperature for 5 hours.. The gas phase detection reaction raw material is less than 3percent. Drop to room temperature and pour into 2L of water.Extracted twice with ethyl acetate, combined organic phases, dried over sodium sulfate, filtered and dried.The obtained crude product (Compound-II-b) was directly reacted in the next step.To the above crude product (Compound-II-b), dichloromethane (400 ml) was added under ice-salt bath.Slowly add 13.6 g of titanium tetrachloride in 60 ml of dichloromethane solution.Control the internal temperature between -10 ° ° C, slowly warmed to room temperature and stirred.The reaction was monitored in the gas phase when the starting material was less than 3percent (about 8 hours).The reaction solution was poured into ice water (about 2 L), and extracted once with dichloromethane.The organic phases were combined, dried over sodium sulfate and filtered and dried then evaporated.The reaction solvent was sparged and flash column chromatography (ethyl acetate: petroleum ether = 1:10).The pale yellow solid compound -III-a, 29.38 g, yield 58percent.In the case of Aluminum chloride (7.40 g, 55.6 mmol) and sodium chloride (2.15 g, 37.1 mmol) were added to a 100 ml flask and heated to 130 C., then 2-bromophenyl-2-chloroethyl ketone (4.60 g , 18.5 mmol) was slowly added, The mixture was stirred at 160 C. for 1 hour. After the reaction, it was cooled to 30 C. and quenched with ice water. ThickAfter adjustment to pH = 5 with hydrochloric acid, the organic phase and aqueous phase were separated and the aqueous phase was extracted with 100 ml of dichloromethane, And the organic phase was collected and washed with 100 ml of water and 100 ml of saturated brine, And the solvent was distilled off under reduced pressure to obtain a crude product. Further, a silica gel column (Petroleum ether / ethyl acetate = 30/1) to obtain 1.60 g (yield 33%) of 7-bromo-1-indanone.A solution of SOCl2 (1.5 eq) and substituted benzoic acid in benzene was refluxed until no more gas evolution was observed. After cooling to room temperature the reaction mixture was concentrated. The concentrate was taken up in dichloroethane and added to a suspension of AlCl3 (1.0 eq) in dichloroethane at 10-20 C. Ethylene was bubbled for 4 hours, then the resulting mixture was stirred for 14 hours and quenched into 4 N HCl. The resulting layers were separated and the aqueous layer was extracted with Et2O (3×250 mL). The combined organic extracts were washed with H2O (3×100 mL), saturated NaHCO3 (3×100 mL) and brine (1×100 mL), then dried over MgSO4 and concentrated.For halogen-containing analogs, the following cyclization procedure was followed: The concentrate containing crude halo substituted phenylpropan-1-one was added to a slurry of AlCl3 (10.0 eq) and NaCl (6.0 eq) at 130 C. The resulting mixture was stirred at 180 C. for 2 hours, then cooled to room temperature and slowly quenched with ice, followed by concentrated HCl. The resulting mixture was extracted with CH2Cl2 (3×300 mL) and the combined extracts were concentrated and purified by column chromatography using hexane:EtOAc (4:1) as eluant to give the desired pure indanone.For alkyl and halogen-containing analogs, the following cyclization procedure was followed: Concentrated sulfuric acid was added to the concentrate containing crude halo and alkyl substituted phenylpropan-1-one and the mixture was stirred at 85 C. for 1 hour. After cooling to room temperature, the reaction mixture was quenched into ice-water. The resulting mixture was extracted with Et2O (3×200 mL) and the combined extracts were washed with H2O (3×200 mL), saturated NaHCO3 (3×200 mL) and brine (1×100 mL), then dried over MgSO4 and concentrated. The pure indanone was obtained after column chromatography using hexane:EtOAc (4:1) as eluant. The desired final cyanoguanidine was thus obtained from this indanone according to the protocols described in general procedure B. 7-Bromo-1-indanone: 9.68 g (31%) of the title amine was obtained from 2-bromo-benzoic acid (30.00 g, 0.15 mol), SOCl2 (16.50 mL, 0.23 mol), AlCl3 (20.00 g, 0.15 mol), an additional AlCl3 (200.00 g, 1.50 mol) and NaCl (52.30 g, 0.89 mol) according to the protocols as outlined in general procedure E. Spectroscopic data: 1H NMR (300 MHz, CDCl3) 2.69-2.79 (m, 2H), 3.04-3.14 (m, 2H), 7.35-7.45 (m, 2H), 7.49-7.55 (m, 1H).37.5 g (109.4 mmol) of methoxymethyltriphenylphosphonium chloride was dispersed in 500 mL of anhydrous THF under nitrogen protection. Cool down to -78 C with liquid nitrogen, 12.3 g (109.4 mmol) of potassium t-butoxide was added in portions. After stirring to room temperature for 30 minutes, the temperature was again lowered to -78C, and 19.5 g (91.2 mmol) of

Molecular Weight:211.05
XLogP3:2.4
Hydrogen Bond Acceptor Count:1
Exact Mass:209.96803
Monoisotopic Mass:209.96803
Topological Polar Surface Area:17.1
Heavy Atom Count:11
Complexity:178
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes