1-bromobut-1-yne

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: Into a suspension of 1.5 g of 66% sodium hydride-paraffin in 20 cc of dimethylformamide was added a solution of 4.5 g of α-phenyl-α-hydroxyphenylacetic acid in 10 cc of dimethylformamide under cooling, and the mixture was stirred for 1 hour. Successively, 5.8 g of butynyl bromide was added thereto and the stirring was continued for 1 hour. The reaction mixture was poured in ice-water, and the resultant was subjected to extraction with ether. The ether extract was washed with an aqueous solution saturated with sodium chloride, and dried over sodium sulfate. Thereafter ether was distilled out and paraffin was removed to obtain 4.0 g of oily 1-butynyl α-phenyl-α-(1-butynyloxy)phenylacetate, nD25 1.5581. under cooling the stirring was continued for 1 hour the resultant was subjected to extraction with ether The ether extract was washed with an aqueous solution saturated with sodium chloride dried over sodium sulfate Thereafter ether was distilled out and paraffin was removed

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 8-chloro-1,7-naphthyridin-3-ol (618 mg, 3.42 mmol) in DMF (11 ml) were added bromobutyne (882 mg, 6.67 mmol), cesium carbonate (3233 mg, 9.92 mmol). The reaction mixture was heated at 50° C. for 0.5 h. It was quenched with water, and light brown precipitate was formed. It was then collected by Buchner funnel to yield 3-(but-2-yn-1-yloxy)-8-chloro-1,7-naphthyridine (550 mg, 74% yield) as light brown solid. MS m/z: 233.1 [M+H]. It was quenched with water light brown precipitate was formed It was then collected by Buchner funnel

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 8-chloro-1,7-naphthyridin-3-ol (618 mg, 3.42 mmol) in DMF (11 ml) were added bromobutyne (882 mg, 6.67 mmol), cesium carbonate (3233 mg, 9.92 mmol). The reaction mixture was heated at 50° C. for 0.5 h. It was quenched with water, and light brown precipitate was formed. It was then collected by Buchner funnel to yield 3-(but-2-yn-1-yloxy)-8-chloro-1,7-naphthyridine (550 mg, 74% yield) as light brown solid. MS m/z: 233.1 [M+H]. It was quenched with water light brown precipitate was formed It was then collected by Buchner funnel

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

Procedure: To a solution containing butynyl bromide (1 g, 7.5 mmol), hydroquinone (827 mg, 7.5 mmol), and K2CO3 (1.04 g, 7.5 mmol) was refluxed for 10 h. Solvent was removed in vacuo and the crude product was dissolved in EtOAc and partitioned with water. Organic layer was separated and washed with water and dried over anhydrous Na2SO4. The solvent was removed in vacuo to obtain the crude product (0.3 g, 25%), which was used for the next step without further purification; LCMS 99%, m/z 162.2 (M+). was refluxed for 10 h Solvent was removed in vacuo the crude product was dissolved in EtOAc partitioned with water Organic layer was separated washed with water dried over anhydrous Na2SO4 The solvent was removed in vacuo

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

Procedure: To a solution containing butynyl bromide (1 g, 7.5 mmol), hydroquinone (827 mg, 7.5 mmol), and K2CO3 (1.04 g, 7.5 mmol) was refluxed for 10 h. Solvent was removed in vacuo and the crude product was dissolved in EtOAc and partitioned with water. Organic layer was separated and washed with water and dried over anhydrous Na2SO4. The solvent was removed in vacuo to obtain the crude product (0.3 g, 25%), which was used for the next step without further purification; LCMS 99%, m/z 162.2 (M+). was refluxed for 10 h Solvent was removed in vacuo the crude product was dissolved in EtOAc partitioned with water Organic layer was separated washed with water dried over anhydrous Na2SO4 The solvent was removed in vacuo

Conditions: temp:56.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 903 g (4.1M) of p-hydroxy cinnamic acid n-butyl ester (see above) are dissolved in 4 liter acetone. 622 g (4.5M) of finely powdered potassium carbonate and 523.5 g (4.4M) freshly distilled butinyl bromide are added. Under stirring the suspension is heated to reflux (temperature in the mixture 56° C.). After refluxing for about 18 hours the starting material is consumed. The yellow suspension is cooled to about 10° C. and filtered. The filtrate is evaporated to dryness in vacuo (about 12 mbar) at 35° C. The yellow oily residue is added with stirring to about 6 liters of water. A white crystalline precipitate is obtained which is isolated by filtration. The solid material is washed with water and dried. It is crystallised from 1 liter of hexane. The product, 805.5 g, is obtained in colourless prisms, mp 38.5° to 39.0° C. From the mother liquor another 183.0 g of product could be isolated. Total yield 988.5 g (93.3% of theory). is heated After refluxing for about 18 hours the starting material is consumed The yellow suspension is cooled to about 10° C. filtered The filtrate is evaporated to dryness in vacuo (about 12 mbar) at 35° C The yellow oily residue is added with stirring to about 6 liters of water A white crystalline precipitate is obtained which is isolated by filtration The solid material is washed with water dried It is crystallised from 1 liter of hexane The product, 805.5 g, is obtained in colourless prisms, mp 38.5° to 39.0° C

Conditions: temp:56.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 903 g (4.1M) of p-hydroxy cinnamic acid n-butyl ester (see above) are dissolved in 4 liter acetone. 622 g (4.5M) of finely powdered potassium carbonate and 523.5 g (4.4M) freshly distilled butinyl bromide are added. Under stirring the suspension is heated to reflux (temperature in the mixture 56° C.). After refluxing for about 18 hours the starting material is consumed. The yellow suspension is cooled to about 10° C. and filtered. The filtrate is evaporated to dryness in vacuo (about 12 mbar) at 35° C. The yellow oily residue is added with stirring to about 6 liters of water. A white crystalline precipitate is obtained which is isolated by filtration. The solid material is washed with water and dried. It is crystallised from 1 liter of hexane. The product, 805.5 g, is obtained in colourless prisms, mp 38.5° to 39.0° C. From the mother liquor another 183.0 g of product could be isolated. Total yield 988.5 g (93.3% of theory). is heated After refluxing for about 18 hours the starting material is consumed The yellow suspension is cooled to about 10° C. filtered The filtrate is evaporated to dryness in vacuo (about 12 mbar) at 35° C The yellow oily residue is added with stirring to about 6 liters of water A white crystalline precipitate is obtained which is isolated by filtration The solid material is washed with water dried It is crystallised from 1 liter of hexane The product, 805.5 g, is obtained in colourless prisms, mp 38.5° to 39.0° C

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

Procedure: Into a suspension of 1.5 g of 66% sodium hydride-paraffin in 20 cc of dimethylformamide was added a solution of 4.5 g of α-phenyl-α-hydroxyphenylacetic acid in 10 cc of dimethylformamide under cooling, and the mixture was stirred for 1 hour. Successively, 5.8 g of butynyl bromide was added thereto and the stirring was continued for 1 hour. The reaction mixture was poured in ice-water, and the resultant was subjected to extraction with ether. The ether extract was washed with an aqueous solution saturated with sodium chloride, and dried over sodium sulfate. Thereafter ether was distilled out and paraffin was removed to obtain 4.0 g of oily 1-butynyl α-phenyl-α-(1-butynyloxy)phenylacetate, nD25 1.5581. under cooling the stirring was continued for 1 hour the resultant was subjected to extraction with ether The ether extract was washed with an aqueous solution saturated with sodium chloride dried over sodium sulfate Thereafter ether was distilled out and paraffin was removed

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 8-chloro-1,7-naphthyridin-3-ol (618 mg, 3.42 mmol) in DMF (11 ml) were added bromobutyne (882 mg, 6.67 mmol), cesium carbonate (3233 mg, 9.92 mmol). The reaction mixture was heated at 50° C. for 0.5 h. It was quenched with water, and light brown precipitate was formed. It was then collected by Buchner funnel to yield 3-(but-2-yn-1-yloxy)-8-chloro-1,7-naphthyridine (550 mg, 74% yield) as light brown solid. MS m/z: 233.1 [M+H]. It was quenched with water light brown precipitate was formed It was then collected by Buchner funnel

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

Procedure: To a solution containing butynyl bromide (1 g, 7.5 mmol), hydroquinone (827 mg, 7.5 mmol), and K2CO3 (1.04 g, 7.5 mmol) was refluxed for 10 h. Solvent was removed in vacuo and the crude product was dissolved in EtOAc and partitioned with water. Organic layer was separated and washed with water and dried over anhydrous Na2SO4. The solvent was removed in vacuo to obtain the crude product (0.3 g, 25%), which was used for the next step without further purification; LCMS 99%, m/z 162.2 (M+). was refluxed for 10 h Solvent was removed in vacuo the crude product was dissolved in EtOAc partitioned with water Organic layer was separated washed with water dried over anhydrous Na2SO4 The solvent was removed in vacuo