5-Bromo-2,3-dihydro-1-benzofuran

white to light yellow crystal powde

Preparation 94 To a chilled (10°C) solution of 10 g (83 mmol) of 2, 3-dihydrobenzofuran in 50 mL of acetic acid, 4 mL (78 mmol) of bromine in 6 mL of acetic acid was added dropwise over a 10 minute period. After 1 hour, the mixture was made basic by cautiously pouring the reaction mixture into saturated/solid aqueous sodium bicarbonate and stirring overnight. The mixture was then extracted with three 100 mL portions of EtOAc. The combined organic layers were washed with two 50 mL portions of saturated aqueous sodium bicarbonate, three 50 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated to afford a yellow oil. The oil was diluted with hexane and passed through a pad (600 mL funnel) of silica gel eluting with hexane to afford a white solid which was diluted with cold (dry ice-acetone) hexane and collected by filtration to afford 4.7 g (28percent) of the title compound as a white solid, m. p. 45°C- 48°C. The filtrate was concentrated to afford 5.1 g of 5-bromo-2, 3-dihydrobenzofuran which was 70percent pure.Compound 2 prepared in step 1), General procedure: A mixture of 8-(4-chlorophenyl)-2-((2, 2, 2- trifluoroethyl)amino)pyrido[4, 3-i/]pyrimi-din-7(d7/)-one (100 mg, 0.28 mmol, 1.0 equiv), 5-bromo-2-methyl-2H-indazole (119 mg, 0.56 mmol, 2.0 equiv.), Cul (5.4 mg, 0.028 mmol, 0.1 equiv.), N1, A2-dimethylcy cl ohexane-l, 2-diamine (8.1 mg, 0.056 mmol, 0.2 equiv.), CS2CO3 (276 mg, 0.847 mmol, 3.0 equiv.) and dioxane (2 mL) was stirred at l00C under N2 atmosphere for l6h. The crude mixture was concentrated under reduced pressure, and the resulting residue was purified by flash column chromatography on silica gel to yield 8-(4- chlorophenyl)-6-(2-methyl-2H-indazol-5-yl)-2-((2, 2, 2- tri fl uoroethyl )am i no)py ri do[-/, 3-6/]pyrimidin-7(6//)-one (Example 123).General procedure: A mixture of 8-(4-chlorophenyl)-2-((2, 2, 2- trifluoroethyl)amino)pyrido[4, 3-i/]pyrimi-din-7(d7/)-one (100 mg, 0.28 mmol, 1.0 equiv), 5-bromo-2-methyl-2H-indazole (119 mg, 0.56 mmol, 2.0 equiv.), Cul (5.4 mg, 0.028 mmol, 0.1 equiv.), N1, A2-dimethylcy cl ohexane-l, 2-diamine (8.1 mg, 0.056 mmol, 0.2 equiv.), CS2CO3 (276 mg, 0.847 mmol, 3.0 equiv.) and dioxane (2 mL) was stirred at l00C under N2 atmosphere for l6h. The crude mixture was concentrated under reduced pressure, and the resulting residue was purified by flash column chromatography on silica gel to yield 8-(4- chlorophenyl)-6-(2-methyl-2H-indazol-5-yl)-2-((2, 2, 2- tri fl uoroethyl )am i no)py ri do[-/, 3-6/]pyrimidin-7(6//)-one (Example 123).General procedure: To a vial were added intermediates 7be19b (1.0 eq), 2-(3-(difluoromethoxy)-5-fluorophenyl)-4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane (1.2 eq), Pd(dppf)Cl2 (5 mol%, 0.05 eq), X-Phos(10 mol%, 0.1 eq), K2CO3 (3.0 eq) and 1, 4-dioxane (3 mL). Then thereaction mixture was stirred under N2 atmosphere at 100 C for 12 h. After completion of the reaction, the resulting mixture wasdiluted with EA and washed with water. The separated aqueousphase was washed with EA. The combined organic layers weredried over MgSO4, filtered, and concentrated in vacuo. The crudemixture was purified by column chromatography on silica gel(petroleum: EA 10:1e5:1) to afford the desired products 7c-19c.

Molecular Weight:199.04
XLogP3:2.8
Hydrogen Bond Acceptor Count:1
Exact Mass:197.96803
Monoisotopic Mass:197.96803
Topological Polar Surface Area:9.2
Heavy Atom Count:10
Complexity:126
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes