7-CHLORO-3-FORMYLINDOLE

General procedure: To the solution of compounds 18a-i (1 equiv) in MeCN wasadded NaH (3 equiv) and 4-Chlorobenzyl chloride (1.5 equiv) atroom temperature. The reaction mixture was stirred at roomtemperature for 4 h. The mixture was extracted with ethyl acetate, washed with brine, dried (Na2SO4), and filtered. The filtrate wasconcentrated in vacuo, and the residue was purified by columnchromatography (silica gel, ethyl acetate/Petroleum ether) to givethe desired product.A solution of Chloro-1H-indole-3-carbaldehyde (100 mg, 0.56 mmol) in MeOH (10 mL) was treated with hydroxylammonium chloride (43 mg, 0.61 mmol), stirred at 23 C for 3 h and treated with nickel(ll) chloride hexahydrate (139 mg, 0.59 mmol). The mixture was cooled to - 78 C, treated portionwise with sodium borohydride (421 mg, 1 1.1 mmol), stirred at -78 C for 1 h before being warmed to RT slowly and stirred until gas evolution had ceased. The mixture was filtered through a syringe filter and evaporated. The residue was dissolved in aqueous 1 % NH3 (30 mL), extracted with EtOAc (3 x 20 mL), dried over anhydrous Na2S04, filtered and evaporated to give the crude ((7-chloro-1 indol-3-yl)methanamine (100 mg, 99%). The product was unstable and was used immediately in the next step without further purification.A suspension of sodium hydride (557 mg, 60% dispersion in mineral oil, 13.9 mmol) in anhydrous THF (25 mL) was treated dropwise with a solution of 7-chloro-1 H-ndoe-3- carbaldehyde (1 .00 g, 5.57 mmol) dissolved in anhydrous THF (5 mL) at 23 C and stirred at 23 C for 15 min. The mixture was treated with Mel (0.45 mL, 7.24 mmol), stirred at 23 C for 1 h and treated with MeOH (10 mL). The solvent was evaporated, the residue was dissolved in water (50 mL), acidified with 1 M HCI to pH 2 and extracted with CH2CI2 (3 x 30 mL). The combined organic layers were dried over anhydrous MgS04, filtered and evaporated. Column chromatography (S1O2; EtOAc/Heptane 30:70 -> 50:50) of the crude gave 7-Chloro-1 -methyl-1 A indole-S-carbaldehyde (800 mg, 74%) as a yellow solid.H NMR (400 MHz, Chloroform-d1 delta = 9.91 (s, 1 H, CHO), 8.18 (dd, J= 7.8, 1.2 Hz, 1 H, H-Ar), 7.54 (s, 1 H, H-Ar), 7.22 (dd, J= 7.7, 1 .2 Hz, 1 H, H-Ar), 7.16 - 7.12 (m, 1 H, H-Ar), 4.14 (s, 3H, CH3) ppm.MS (ESI+, H20/MeCN) /z {%): 194.2 (100, [M + H]+).

Molecular Weight:179.60
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:179.0137915
Monoisotopic Mass:179.0137915
Topological Polar Surface Area:32.9
Heavy Atom Count:12
Complexity:185
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes