N-(2,3-dihydroinden-1-ylidene)hydroxylamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of p-toluenesulfonyl chloride (266 g) in pyridine (300 ml) was added dropwise to a stirred solution of 2,3-dihydro-1-hydroxyimino-1H-indene (100.8 g) in pyridine (600 ml) at 0°-5°. The mixture was stirred for 3 hours at 0°, then was poured into water and the title compound filtered. This was washed several times with water and air-dried. the title compound filtered This was washed several times with water air-dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of p-toluenesulfonyl chloride (266 g) in pyridine (300 ml) was added dropwise to a stirred solution of 2,3-dihydro-1-hydroxyimino-1H-indene (100.8 g) in pyridine (600 ml) at 0°-5°. The mixture was stirred for 3 hours at 0°, then was poured into water and the title compound filtered. This was washed several times with water and air-dried. the title compound filtered This was washed several times with water air-dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-indanone (100 g), hydroxylamine HCl (183 g), potassium carbonate (183 g), methanol (1700 ml) and water (170 ml) was heated at reflux for 18 hours, then cooled and poured into water. The title compound was filtered, washed with water and air-dried. was heated at reflux for 18 hours cooled The title compound was filtered washed with water air-dried

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 12 l four-necked flask fitted with a mechanical stirrer, a reflux condenser and a thermometer was placed 3.6 l of deionized water. Hydroxylamine hydrochloride was added. A clear, colorless solution formed (pH 2.5) to which was added 475 ml of 50% sodium hydroxide which had been diluted to 2.4 l with deionized water (pH 6.2). 1-Indanone was dissolved in 2.4 l of 3A anhydrous ethanol and added to the flask. The slightly turbid solution was heated at reflux for 15 minutes. A white solid started to precipitate at 39° C. The mixture was cooled to room temperature and then in an ice-water bath. The product was filtered off and washed with three 2 l portions of chilled water. The product was dried in a vacuum oven at 46° C. A white fluffy solid was obtained. In a 12 l four-necked flask fitted with a mechanical stirrer, a reflux condenser A clear, colorless solution formed (pH 2.5) to which added to the flask The slightly turbid solution was heated at reflux for 15 minutes to precipitate at 39° C The product was filtered off washed with three 2 l portions of chilled water The product was dried in a vacuum oven at 46° C A white fluffy solid was obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In Step 1 a 1-indanone is treated with a hydroxylamine and a base to produce a 1-indanone oxime. In Step 2 the oxime is hydrogenated to produce a corresponding primary amine, both R and S forms. In Step 3 the primary amine is then added to D-N-acetyl-3,4-dimethoxyphenylalanine in alcohol to produce the (R,R) and (R,S) salts of the primary amine. The (R,S) salt crystallizes first and the (R,R) salt is soluble. These are separated by filtration. The mother liquor, on concentrating and cooling precipitates the desired R,R isomer in high yield and optical purity. In Step 4 a solution of R,R isomer is treated with a base to produce the R form of the primary amine. In Step 5 the R primary amine is reacted with a tertiary amine and 6-chloropurineriboside to produce the adenosine compounds of Formula I of the present invention, for example, N6 -[1-(R)-indanyl]adenosine. ##STR4##

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Indanone (4.00 g, 30.3 mmol) and hydroxylamine hydrochloride (5.26 g, 75.7 mmol) were dissolved in a mixture of methanol (40 ml) and pyridine (10 ml) and stirred for 3 hours at ambient temperature. The reaction mixture was concentrated in vacuo and the resultant residue was diluted with 1N HCl (100 ml) and extracted three times with methylene chloride. The organic layer was dried over MgSO4 and concentrated in vacuo to provide 4.13 g (93% yield) of the desired 1-indanone oxime as white needles. The reaction mixture was concentrated in vacuo the resultant residue was diluted with 1N HCl (100 ml) extracted three times with methylene chloride The organic layer was dried over MgSO4 concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Indanone oxime (7.02 g, 0.048 moles), pyridine (250 ml) and acetic anhydride (170 ml) were stirred and heated under nitrogen at reflux for 16.5 hours. The cooled mixture was evaporated in vacuo and the residue agitated thoroughly with 1N sodium carbonate solution and ether (250 ml each). The liquid was filtered through filter-aid and the black solid treated again with sodium carbonate/ether and filtered. The combined ether extracts and washes were dried (MgSO4) and evaporated to a black-orange oil (8.6 g). This was applied to a column of basic alumina, allowed to stand for 2.5 hours and eluted with ethyl acetate/hexane 1:2 v/v. The appropriated fractions were evaporated to leave a crude solid (3 g). This was recrystallized from ethyl acetate/hexane to give the title product, mp. 139° C., (1.44 g, 17%) with the same IR spectrum as in Example 1. heated under nitrogen at reflux for 16.5 hours The cooled mixture was evaporated in vacuo The liquid was filtered through filter-aid the black solid treated again with sodium carbonate/ether filtered The combined ether extracts and washes were dried (MgSO4) evaporated to a black-orange oil (8.6 g) eluted with ethyl acetate/hexane 1:2 v/v The appropriated fractions were evaporated to leave a crude solid (3 g) This was recrystallized from ethyl acetate/hexane