indolin-6-ol

NaBH(CN)2, 3-dihydro-1H-indol-6-ole General procedure: Procedure E: Reduction of indoles to indolines. Method I: NaBH3CN (4.23 mmol) was added portion wise over 10 min at 0 C to a solution of alpha, beta-unsaturated system or to an indole (1.06 mmol) in AcOH (7.1 mL) and the mixture was stirred at room temperature from 1 h to overnight. Water (3 mL) was added and the solvent was removed under reduce pressure. The residue was dissolved in EtOAc and washed with saturated NaHCC>3 and brine, dried over MgS04 and evaporated to give the indoline. The indoline hydrochloride was obtained after dissolving an indoline in EtOAc followed by extraction with 2N HC1. The aqueous phase was evaporated to give the reduced salt. An alternative method for the preparation of the indoline hydrochloride involved addition of HC1 gas to a solution of indoline in dry ether.3-(2-(Methoxycarbonyl)ethyl) indolin-5-yl ethylmethylcarbamate, AN-669. Compound AN-669 prepared from AN-785 or AN- 789 by procedure E, was stirred at room temperature over night, was isolated as a white crystals in 23% yield, mp 108-113 C. *H- NMR (300 MHz, D20) ppm delta 7.52 (d, J = 8.4 Hz, 1H, H-4), 7.17-7.25 (m, 2H, H-7+H-6), 4.01-4.16 (m, 1H, H-2'), 3.66 (s, 3H, H-17), 3.55-3.67 (m, 2H, H-2+H-3), 3.31-3.52 (m, 2H, H- l l), 3.08+2.95 (s, 3H, H-13), 2.48-2.52 (m, 2H, H-15), 2.14 (ddd, J = 21.5, 14.7, 7.8 Hz, 1H, H-14), 1.91 (ddd, J = 21.5, 14.7, 7.8 Hz, 1H, H-14), 1.09-1.24 (m, 3H, H-12); 13C- NMR (75 MHz, D20) ppm delta 176.03, 152.30, 145.98, 140.24, 126.94, 122.68, 119.33, 115.81 , 51.57, 51.28, 44.24, 40.52, 33.64, 33.91, 30.94, 27.54, 11.54, 12.19.General procedure: The title compound was prepared according to General Procedure G from methyl indoe~6- carboxylate (200 mg, 1.14 mmo). The crude product was purified b Combifiash silica gel chromatography (0-30% of EtOAc in hexane), which provided 153 mg (76%) of the title compound as a colorless solid; NMR (400 MHz, CD ) delta - 7.51 (dd, J = 1, 5, 7.6 Hz, 1 H), 7.39 (d, J ~ 15 Hz, 1 H), 7.19 (d, J = 7.6 Hz, 1 H), 3.89 (s, 3 H), 3.67 ( , J = 8, 5 Hz, 2 H), 3.12 (t, J *= 8, 5 Hz, 2 H). General Procedure 6; Reduction of indole in indolin-e. To the solution of indole (1 eq.) in AcOH (C; 0, 5 rnmo) at room temperature was added N38H3CN (3 eq.). The reaction was stirred at the same temperature for 2~4h, The completion of the reaction was monitored by HPLC. Upon completion, H2O was added and the reaction mixture was concentrated to dryness. H2O was added to the crude residue and the reaction mixture was extracted with EtOAc. The combined organic layers were washed with saturated aqueous NaHCCh, brine and dried over a^SQ^ Filtratio and removal of the solvent provided the desired product, which was used without further purification or purified by Combiflash silica gel chromatography to give the corresponding products.Compound 94 was synthesized using a slightly modified protocol published by Maiti and Buchwald.4 An oven or flame dried, microwave glass tube was charged with a magnetic stir bar, compound 90 (150 mg, 1.11 mmol), 93 (272 mg, 1.11 mmol), Cul (21 mg, 0.11 mmol), 2- picolinic acid (27 mg, 0.22 mmol), and anhydrous K3P04 (427 mg, 2.22 mmol). The glass tube was evacuated under vacuum and backfilled with N2 5 times before the tube was immediately sealed with a Teflon cap. Anhydrous DMSO (2 mL) was delivered via a syringe. The reaction was then heated to 85 C and stirred for 18 h. After cooling to rt, the reaction mixture was diluted with 10 mL DI water and extracted with DCM (4 x 25 mL). The combined organic layers were washed with brine and dried over anhydrous Na2S04, then concentrated in vacuo. The residue was purified by flash column chromatography with silica gel (25 g), using DCM/Hexane as eluent to give compound 94 (227 mg, 81%) as a colorless oil.Compound 90 (0.8 g, 5.92 mmol) was suspended in 10 mL DI water, to which Acetic anhydride (2.24 mL, 23.67 mmol) was added dropwise. The reaction mixture was placed in an (0886) ultrasonication bath for 1 min, then was stirred in a water bath (50 C) for 10 min. The resulting solution was stirred overnight at rt. After which, the solid was collected via vacuum filtration and washed with small portions of DI water. The product was left in the funnel and air dried overnight to afford compound 96 (929 mg, 89%) as a light gray solid, which was used for the next step without further purification.

Molecular Weight:135.16
XLogP3:1.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Exact Mass:135.068413911
Monoisotopic Mass:135.068413911
Topological Polar Surface Area:32.3
Heavy Atom Count:10
Complexity:126
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes