Step 2: 8-Bromo-lH-indole-2, 3-dioTo the concentrated sulfuric acid (70 mL) at 60 °C was added N-(2-bromo- phenyl)-2-hydroxyimino-acetamide (7 g, 0.028 mol). The temperature was raised to 90 °C and maintained for 3 h. The reaction mixture was added to ice cold water to get yellow precipitate. The precipitate was filtered and dried to get the title compound as a yellow solid [6.0 g, 92percent]. 1H NMR (300 MHz, DMSO-dIn a 250 mL four-necked flask, 25 mL of concentrated sulfuric acid was added, 5 g (0.021 mol) of N- (2-bromophenyl) -2-isonitrosonanilide was added in portions to a temperature of 60 ° C, Feeding process temperature in the 60-65 , Feeding complete, The temperature of the reaction was slowly raised to 80 ° C and the reaction was stirred for 5 minutes.TLC monitoring, Reaction completed, The reaction solution was quenched with vigorous stirring into 100 mL of crushed ice, After stirring for 0.5 hour, Standing for 10 minutes, filter, And dried to obtain 4.19 g of 7-bromo isatin as a yellow solid (yield 90percent).40 mL of concentrated sulfuric acid was added to a 100 mL round bottom flask, 13.4 g of a yellow solid was slowly added to concentrated sulfuric acid at 50 ° C, The reaction was complete at 65 ° C for 30 min.After completion of the reaction, the mixture was cooled to room temperature, The reaction mixture was then poured into an ice-water mixture, Stirring 30min, A red solid was obtained by suction filtration, The empty oven under dry, To give 11.4 g of 7-bromo-Π-induced dione, Yield 84percent.As a red solid.7-bromo-1 /-/-indole-2, 3-dioneTo sulfuric acid (1 .6 L) at 60°C, was added A/-(2-bromophenyl)-2- (hydroxyimino)ethanamide (86 g, 356.8 mmol) portionwise over 30 minutes such that the temperature of the reaction mixture did not exceed 65°C. The mixture was heated to 80°C for 15 minutes, cooled to 70°C, and poured onto crushed ice. The ice mixture was allowed to stand for 1 h before the solids were collected by filtration. The crude solids were washed with water and dried. The crude material was dissolved in a solution of NaOH in water at 60°C and acidified with acetic acid. After standing for 0.5 h and cooling to 35°C, the solids were collected by filtration and washed with a minimal amount of water. The filter cake was set aside. The filtrate was acidified with concentrated HCI and allowed to stand for 2 h at 5°C. Solids were collected by filtration and washed with water. The combined filter cakes were dried in vacuo to afford 7-bromo-1 H-indole-2, 3-dione (53 g, 66percent yield). Chloral hydrate (5.01 g, 30.2 mmol) and Na144B. 7-bromoisatin.; N-(2-Bromo-phenyl)-2-hydroxyimino-acetamide from example 144A (7.8 g, 32 mmol) was added in small portions to 41 mL of sulfuric acid at 60° C. so as to keep the reaction temperature under 80° C. After addition the temperature was raised to 80° C. and the reaction was stirred at this temperature for 1 hr. The mixture was than cooled to room temperature and poured onto crushed ice. The red solids formed were isolated by filtration, rinsed thoroughly with water and dried in vacuo. 6.36 g of solid was obtained (88percent). NMR General procedure: Indoles 1 (0.5 mmol), DMSO (3mL) and IStep-1: Synthesis of Via: To a solution of chloral hydrate (5.28 g, 31.9 mmol) in deionized water (90 mL), sodium sulphate (53.6 g, 377.9 mmol), 2- bromoaniline (5 g, 29.11 mmol), were added sulphuric acid (20 mL) followed by hydroxylamine hydrochloride (6.66 g, 87.2 mmol) and the whole mixture was heated to 130 C for 30 min. The mixture was cooled to room temperature, poured on ice-water mixture and extracted with ethylacetate. Organic layer was washed with brine, dried over sodium sulphate and evaporated under reduced pressure. Crude obtained was taken for the next step without any purification. (0457) [000169] Step-2: Sulphuric acid (50 mL) was added to the crude obtained in stepl and the mixture was heated to 70 °C for lh. After the complete consumption of starting material, reaction mixture was poured over ice, and extracted with ethyl acetate (2 x 200 mL). Organic layer was washed with brine, dried over sodium sulphate and evaporated under reduced pressure. Crude was purified by silica gel column chromatography by using 20percent ethyl acetate in pet ether for elution to get 2.5 g of Via.
skype
12YRS 
