Acetic Acid → Benzenesulfonamide

A solution of 0.42 g (2.0 mmol) of 6-hydroxymethyl-3-methysulfanyl-1,3-dihydro-indol-2-one in DMF (10 mL) was treated with 0.32 g (2.1 mmol) of t-h. The solution was diluted with 50 mL of hexane and 50 mL of EtOAc, washed with brine, dried over MgSO4 and concentrated to give 0.28 g (43%) of 3-methylsulfanyl-6-(t-butyidimethylsilyloxy)methyl-1,3-dihydro-indol-2-one as a clear oil which crystallised upon storage at rt: 1H NMR (DMSO-d6): δ 0.01 (s, 6H), 0.97 (s, 9H), 2.00 (s, 3H), 4.52 (s, 1H), 4.72 (s, 2H), 6.85 (s, 1H), 6.96 (d, J=7.7 Hz, 1H), 7.25 (d, J=7.7 Hz, 1H), 10.54 (s, 1H). A solution of 0.28 g (0.86 mmol) of 3-methylsulfanyl4-(t-butyidimethylsilyloxy)methyl-1,3-dihydro-indol-2-one in THF (10 mL) was stirred with saturated ammonium chloride solution (10 mL), and activated zinc dust (2 g) was added. The mixture was stirred 16 h at rt. The organic phase was separated, dried over MgSO4 and concentrated to give 0.32 g of impure 4-(t-butyidimethylsilyloxy)methyl-1,3-dihydro-indol-2-one as a gummy white solid: 1H NMR (DMSO-d6): δ 0.04 (s, 6H), 0.87 (s, 9H), 3.39 (s, 2H), 4.62 (s, 2H), 6.75 (s, 1H), 6.81 (d, J=7.5 Hz, 1H), 7.10 (d, J=7.5 Hz, 1H), 10.30 (bs, 1H). A solution of 0.32 g (1.2 mmol) of 4-(t-butyidimethylsilyloxy)methyl-1,3-dihydro-indol-2-one in DMF dimethylacetal (3 mL) was heated to 100° C. for 0.75 h. The excess DMF dimethylacetal was removed under high vacuum, and the resulting dark oil was chromatographed on silica gel, eluting with EtOAc/MeOH (98:2), to give 0.16 g (41%) of 3-dimethylaminomethylene-6-(t-butyldimethylsilyloxy)methyl-1,3-dihydro-indol-2-one (11:9 mixture of E and Z isomers) as a yellow solid: 1H NMR (DMSO-d6, peak areas normalized using the combined peak areas for δ 9.88 and 9.66 as 1H): δ 0.21 (s, 2.70H), 0.34 (s, 3.3H), 0.85 (s, 4.05H), 0.86 (s, 4.95H), 3.25 (s, 2.70H), 3.30 (s, 3.30H), 4.58 (s, 0.9H), 4.59 (s, 1.1H), 6.64-6.71 (m, 2H), 7.16 (d, J=7.7 Hz, 0.45H), 7.29 (d, J=8.3 Hz, 0.55H), 7.33 (s, 0.55H), 7.47 (s, 0.45H), 9.88 (s,0.55H) 9.96 (s, 0.45H); APCI−MS m/z 331 (M+1)+. A solution of 0.334 g (1.00 mmol) of 3-dimethylamino-methylene-6-(t-butyldimethylsilyloxy)methyl-1,3-dihydro-indol-2-one in 2-methylpropanol (3 mL) was treated with 0.174 g (1.00 mmol) of sulfanilamide and 0.25 g (4.0 mmol) of acetic acid. The solution was refluxed for 3 h and cooled to rt. The resulting yellow precipitate was isolated by filtration, washed with ethanol and dried to yield 0.134 g (29%) of 6-([t-butyldimethyl-silyloxy)methyl-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-amino]-benzenesulfonamide (Z isomer).: 1H NM R (DMSO-d6): δ 0.05 (s, 6H), 0.87 (s, 9H), 4.65 (s, 2H), 6.81 (s, 1H), 6.85 (d, J=8.0 Hz, 1H), 7.23 (s, 2H), 7.49-7.51 (m, 3H), 7.75 (d, J=8.4 Hz, 2H), 8.56 (d, J=12.3 Hz, 1H), 10.52 (s, 1H), 10.76 (d, J=12.3 Hz, 1H); APCI−MS m/z 458 (M−H)−. To a solution of 0.125 g (2.80 mmol) of 6-([t-butyidimethylsilyloxy]methyl-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-amino]-benzenesulfonamide in THF (5 mL) was added 0.27 mL of a 1 M solution of t-butylammonium fluoride in THF, and the mixture was stirred at rt for 1 h. The resulting yellow precipitate was isolated by filtration, washed with THF and dried. Chromatographic purification of the solid on silica gel, eluting with a hexane to EtOAc gradient, gave 0.053 g (55%) of the title compound: 1H NMR (DMSO-d6): δ 4.43 (d, J=5.8 Hz, 2H), 5.08 (t, J=5.8 Hz, 1H), 6.82 (s, 1H), 6.85 (d, J=8.2 Hz, 1H), 7.23 (s, 2H), 7.50 (d, J=7.5 Hz, 2H), 7.74 (d, J=8.7 Hz, 3H), 8.56 (d, J=12.2 Hz, 1H), 10.54 (s, 1H), 10.75 (d, J=12.1 Hz, 1H); APCI−MS m/z 345 (M−H)−. Anal. Calcd for C16H15N3O4S.0.5 H2O: C, 54.43, H, 4.55; N, 11.86, S, 9.05. Found C, 54.47, H, 4.63; N, 11.66; S, 8.86.

1. temperatureThe solution was refluxed for 3 h
2. customThe resulting yellow precipitate was isolated by filtration
3. washwashed with ethanol
4. customdried

ORD record

ord-a95bc5c3d0ce4b7e8f8c622c1257c588

Source dataset

uspto-grants-2002_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06387919B1