4-BROMO-6-METHOXYINDOLE

(b) 4-Bromo-6-methoxy-1 H-indoleN-(3-Bromo-5-methoxy-phenyl)-N-hydroxy-acetamide (360 mg, 1.384 mmol) was dissolved in vinyl acetate (1 .92 mL, 20.8 mmol), and Li4-bromo-6- methoxy- IH- indole (177-1) (360 mg, 1.6 mmol) was dissolved in DMF and cooled to 0 C. NaH (60%, 128 mg, 3.2 mmol) was then added in portions followed by the addition of tert- butyl (2-bromoethyl)carbamate (177-2) (428 mg, 1.9 mmol). The mixture was allowed warm to r.t. and stirred for l2h, then poured into water and extracted with EA. The organic phase was separated and washed with sat. aq. NaCl, dried over Na2S04, filtered, concentrated and purified by flash chromatography to afford the title compound (380 mg yield 65%). 1 H NMR (600 MHz, Chloroform- ) d 7.26 (s, 1H), 7.00 (t, J = 2.4 Hz, 2H), 6.47 (d, J = 3.2 Hz, 1H), 4.52 (s, 1H), 4.19 (t, J = 6.0 Hz, 2H), 3.85 (s, 3H), 3.47 (q, J = 6.1 Hz, 2H), 1.43 (s, 9H). h?/A mixture of 4-bromo-6-fluoro-1H-indole (36 mg, 0.168 mmol), bis(pinacolato)diboron (90 mg, 0.350 mmol), potassium acetate (41 mg, 0.420 mmol) and PdCI2(dppf) (23 mg, 0.028 mmol) in dioxane (1 mL) was heated in a sealed tube at 100C for 3 h. On cooling, intermediate XL (40 mg, 0.140 mmol) in dioxane (1 mL), tetrakis(triphenylphosphine)palladium(0) (16 mg, 0.014 mmol) and Na2C032M (0.21 mL) were added. The reaction mixture was heated at 100C for 19h. On cooling, the mixture was purified by flash column chromatography, first (5% to 10% EtOAc in DCM) and second by prep-HPLC to give the final product Example 45 as a white solid (12 mg). LC-MS1 , tR= 4.04 min. MS: 385.2 [M+H]+ 1 H NMR (300 MHz, DMSO) delta 1 1.30 (s, 1 H), 7.79 (d, J = 1 1.4 Hz, 1 H), 7.44 (s, 1 H), 7.26 (d, J = 15.4 Hz, 2H), 5.34 (s, 1 H), 4.47 (dd, J = 27.0, 10.9 Hz, 2H), 4.05 (d, J = 8.2 Hz, 1 H), 3.93 (t, J = 10.1 Hz, 2H), 3.72 (s, 1 H), 3.58 (s, 1 H), 3.20 (dd, J = 24.7, 13.8 Hz, 3H), 1.52 (s, 7H). Example 46 was synthesized following a similar synthetic route to the one used for Example 45, by Suzuki coupling of intermediate XL with 4-bromo-6-methoxy-1 /-/-indole in the presence of bis(pinacolato)diboron and palladium catalyst. LC-MS1 , tR= 3.38 min. MS: 397.2 [M+H]+ 1 H NMR (300 MHz, DMSO) delta 1 1.03 (s, 1 H), 7.60 (d, J = 2.2 Hz, 1 H), 7.29 (s, 1 H), 7.10 (s, 1 H), 7.02 (s, 1 H), 5.44 (s, 1 H), 4.59 - 4.35 (m, 2H), 4.07 (s, 1 H), 3.92 (t, J = 9.7 Hz, 2H), 3.81 (s, 3H), 3.77 - 3.65 (m, 1 H), 3.57 (s, 1 H), 3.22 (s, 2H), 1.52 (s, 6H).(b) 4-Bromo-6-methoxy-1 H-indoleN-(3-Bromo-5-methoxy-phenyl)-N-hydroxy-acetamide (360 mg, 1.384 mmol) was dissolved in vinyl acetate (1 .92 mL, 20.8 mmol), and Li2PdCI4 (18.2 mg, 69 muiotaetaomicronIota) was added. The reaction mixture was stirred for 3 hours at 60 C. The reaction mixture was diluted with EtOAc and brine; the organic layer was separated and concentrated under reduced pressure to give a solid, which was dissolved in 20 mL of MeOH. 1 N aqueous NaOH (2.61 mL, 2.61 mmol) was added, and the reaction was stirred for two hours at room temperature. The reaction mixture was quenched by addition of 2 N aqueous HCI (1.3 mL, 2.6 mmol), followed by addition of 500 mg of Na2C03. After addition of 50 mL of EtOAc, the organic layers were separated, dried over Na2S04, filtered, and concentrated. The residue was purified by column chromatography (20 g Si02, EtOAc/heptane in a gradient from 0/100 to 1/4) to yield the title compound as a liquid (145 mg, 46% over 2 steps). H-NMR (600 MHz; DMSO-d6): 1 1.26 (brs, 1 H), 7.31 (dd, 1 H), 6.93 (d, 1 H), 6.90 (d, 1 H), 6.29 (dd, 1 H), 3.78 (s, 3H).

Molecular Weight:226.07
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:224.97893
Monoisotopic Mass:224.97893
Topological Polar Surface Area:25
Heavy Atom Count:12
Complexity:165
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes