but-3-enenitrile

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirring mixture of ethyl 6-bromoimidazo[1,2-a]pyridine-3-carboxylate (24s) (500 mg, 1.86 mmol), allyl cyanide (224 uL, 2.79 mmol), tris(dibenzylideneacetone)dipalladium(0) (26 mg, 0.028 mmol), [(t-Bu)3PH]BF4 (16 mg, 0.056 mmol), and N,N-dicyclohexylmethylamine (433 μL, 2.04 mmol) in anhydrous 1,4-dioxane (6 mL) was heated at 95° C. overnight. The reaction was cooled to room temperature and filtered. The solvent was concentrated. The crude product was purified by silica chromatography to give ethyl 6-(3-cyanoprop-1-enyl)imidazo[1,2-a]pyridine-3-carboxylate (24v). MS m/z 256.4 (M+1)+. The reaction was cooled to room temperature filtered The solvent was concentrated The crude product was purified by silica chromatography

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

Procedure: The starting material is prepared as follows: To the solution of 1,134 g of bromine in 1,400 ml of ethyl acetate 472 g of allyl cyanide are added dropwise while stirring for 90 minutes at -10°-0°. The resulting solution of 3,4-dibromobutyronitrile is added all at once to the solution prepared from 705 g of catechol and 1,987 g of anhydrous potassium carbonate in 5,000 ml of refluxing ethyl acetate, while stirring at 35° under nitrogen. The mixture is refluxed for 4 hours and stirred overnight at room temperature. It is filtered, the residue washed with 2,000 ml of ethyl acetate, the filtrate evaporated, the residue distilled and the fraction boiling at 138°/1.4-131°/1.1 mm Hg collected, to yield the 1,4-benzodioxan-2-yl-acetonitrile. The starting material is prepared while stirring at 35° under nitrogen The mixture is refluxed for 4 hours stirred overnight at room temperature It is filtered the residue washed with 2,000 ml of ethyl acetate the filtrate evaporated the residue distilled the fraction boiling at 138°/1.4-131°/1.1 mm Hg collected

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirring mixture of ethyl 6-bromoimidazo[1,2-a]pyridine-3-carboxylate (24s) (500 mg, 1.86 mmol), allyl cyanide (224 uL, 2.79 mmol), tris(dibenzylideneacetone)dipalladium(0) (26 mg, 0.028 mmol), [(t-Bu)3PH]BF4 (16 mg, 0.056 mmol), and N,N-dicyclohexylmethylamine (433 μL, 2.04 mmol) in anhydrous 1,4-dioxane (6 mL) was heated at 95° C. overnight. The reaction was cooled to room temperature and filtered. The solvent was concentrated. The crude product was purified by silica chromatography to give ethyl 6-(3-cyanoprop-1-enyl)imidazo[1,2-a]pyridine-3-carboxylate (24v). MS m/z 256.4 (M+1)+. The reaction was cooled to room temperature filtered The solvent was concentrated The crude product was purified by silica chromatography

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirring mixture of ethyl 6-bromoimidazo[1,2-a]pyridine-3-carboxylate (24s) (500 mg, 1.86 mmol), allyl cyanide (224 uL, 2.79 mmol), tris(dibenzylideneacetone)dipalladium(0) (26 mg, 0.028 mmol), [(t-Bu)3PH]BF4 (16 mg, 0.056 mmol), and N,N-dicyclohexylmethylamine (433 μL, 2.04 mmol) in anhydrous 1,4-dioxane (6 mL) was heated at 95° C. overnight. The reaction was cooled to room temperature and filtered. The solvent was concentrated. The crude product was purified by silica chromatography to give ethyl 6-(3-cyanoprop-1-enyl)imidazo[1,2-a]pyridine-3-carboxylate (24v). MS m/z 256.4 (M+1)+. The reaction was cooled to room temperature filtered The solvent was concentrated The crude product was purified by silica chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5′-bromospiro[1,3-dioxane-2,3′-indol]-2′(1′H)-one (2.00 g, 7.04 mmol) and benzyltrimethylammonium hydroxide (40% aqueous solution, 0.768 mL, 1.69 mmol, 0.24 mole %) in abs. EtOH (32 mL) was added allyl cyanide (1.42 mL, 17.6 mmol, 2.5 eq) all at one time at room temperature and the mixture was heated at 80° C. for 2.5 hr. Additional benzyltrimethyl-ammonium hydroxide (0.77 mL) was added and the heating continued another 24 hr. The reaction was cooled to room temperature and poured into H2O (100 mL). The reaction mixture was extracted with EtOAc (3×). The combined organic extracts were concentrated. The crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH (97/2/1) to give the title compound as a white solid (0.299 g, 16% ). Anal. Calc'd for: C15H15BrN2O3: C, 51.3; H, 4.3; N, 7.98. Found: C, 51.55; H, 4.47; N 7.99. NMR (300 Mz, DMSO-d6): consistent. MS: (ES+) m/z 350/352 [M+]; one Br pattern observed. m.p.: 112-113° C. The reaction was cooled to room temperature The reaction mixture was extracted with EtOAc (3×) The combined organic extracts were concentrated The crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH (97/2/1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5′-bromospiro[1,3-dioxane-2,3′-indol]-2′(1′H)-one (2.00 g, 7.04 mmol) and benzyltrimethylammonium hydroxide (40% aqueous solution, 0.768 mL, 1.69 mmol, 0.24 mole %) in abs. EtOH (32 mL) was added allyl cyanide (1.42 mL, 17.6 mmol, 2.5 eq) all at one time at room temperature and the mixture was heated at 80° C. for 2.5 hr. Additional benzyltrimethyl-ammonium hydroxide (0.77 mL) was added and the heating continued another 24 hr. The reaction was cooled to room temperature and poured into H2O (100 mL). The reaction mixture was extracted with EtOAc (3×). The combined organic extracts were concentrated. The crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH (97/2/1) to give the title compound as a white solid (0.299 g, 16% ). Anal. Calc'd for: C15H15BrN2O3: C, 51.3; H, 4.3; N, 7.98. Found: C, 51.55; H, 4.47; N 7.99. NMR (300 Mz, DMSO-d6): consistent. MS: (ES+) m/z 350/352 [M+]; one Br pattern observed. m.p.: 112-113° C. The reaction was cooled to room temperature The reaction mixture was extracted with EtOAc (3×) The combined organic extracts were concentrated The crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH (97/2/1)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: n-Butyllithium (2.5 M in THF, 33 mL, 82 mmol) was added dropwise to a solution of diisopropylamine (9.0 g, 90 mmol) in THF at −78° C. The reaction mixture was stirred at −78° C. for 1 hour. To the mixture was added a solution of 3-butenenitrile (5.0 g, 74.6 mmol) in THF (30 mL) dropwise at −78° C. The resultant mixture was stirred at the temperature for 1 hour, then a solution of ethyl bromoacetate (13.7 g, 82.06 mmol) in THF (30 mL) was added dropwise at −78° C. to the reaction mixture. The reaction mixture was stirred at −78° C. for an additional 1 hour. The reaction mixture was poured into a solution of saturated aqueous ammonium chloride and extracted with tert-butyl methyl ether (3×300 mL). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford the crude product residue. The crude product residue was purified by silica gel chromatography (ethyl acetate/petroleum ether) to afford ethyl 3-cyanopent-4-enoate as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 5.83-5.71 (m, 1H), 5.53-5.49 (m, 1H), 5.36-5.33 (m, 1H), 4.20 (q, J=7.2 Hz, 2H), 3.79-3.71 (m, 1H), 2.81-2.73 (m, 1H), 2.69-2.61 (m, 1H), 1.28 (t, J=7.2 Hz, 3H). The reaction mixture was stirred at −78° C. for an additional 1 hour extracted with tert-butyl methyl ether (3×300 mL) dried over sodium sulfate filtered concentrated under reduced pressure to afford the crude product residue The crude product residue was purified by silica gel chromatography (ethyl acetate/petroleum ether)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: n-Butyllithium (2.5 M in THF, 33 mL, 82 mmol) was added dropwise to a solution of diisopropylamine (9.0 g, 90 mmol) in THF at −78° C. The reaction mixture was stirred at −78° C. for 1 hour. To the mixture was added a solution of 3-butenenitrile (5.0 g, 74.6 mmol) in THF (30 mL) dropwise at −78° C. The resultant mixture was stirred at the temperature for 1 hour, then a solution of ethyl bromoacetate (13.7 g, 82.06 mmol) in THF (30 mL) was added dropwise at −78° C. to the reaction mixture. The reaction mixture was stirred at −78° C. for an additional 1 hour. The reaction mixture was poured into a solution of saturated aqueous ammonium chloride and extracted with tert-butyl methyl ether (3×300 mL). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford the crude product residue. The crude product residue was purified by silica gel chromatography (ethyl acetate/petroleum ether) to afford ethyl 3-cyanopent-4-enoate as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 5.83-5.71 (m, 1H), 5.53-5.49 (m, 1H), 5.36-5.33 (m, 1H), 4.20 (q, J=7.2 Hz, 2H), 3.79-3.71 (m, 1H), 2.81-2.73 (m, 1H), 2.69-2.61 (m, 1H), 1.28 (t, J=7.2 Hz, 3H). The reaction mixture was stirred at −78° C. for an additional 1 hour extracted with tert-butyl methyl ether (3×300 mL) dried over sodium sulfate filtered concentrated under reduced pressure to afford the crude product residue The crude product residue was purified by silica gel chromatography (ethyl acetate/petroleum ether)

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirring mixture of ethyl 6-bromoimidazo[1,2-a]pyridine-3-carboxylate (24s) (500 mg, 1.86 mmol), allyl cyanide (224 uL, 2.79 mmol), tris(dibenzylideneacetone)dipalladium(0) (26 mg, 0.028 mmol), [(t-Bu)3PH]BF4 (16 mg, 0.056 mmol), and N,N-dicyclohexylmethylamine (433 μL, 2.04 mmol) in anhydrous 1,4-dioxane (6 mL) was heated at 95° C. overnight. The reaction was cooled to room temperature and filtered. The solvent was concentrated. The crude product was purified by silica chromatography to give ethyl 6-(3-cyanoprop-1-enyl)imidazo[1,2-a]pyridine-3-carboxylate (24v). MS m/z 256.4 (M+1)+. The reaction was cooled to room temperature filtered The solvent was concentrated The crude product was purified by silica chromatography

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirring mixture of ethyl 6-bromoimidazo[1,2-a]pyridine-3-carboxylate (24s) (500 mg, 1.86 mmol), allyl cyanide (224 uL, 2.79 mmol), tris(dibenzylideneacetone)dipalladium(0) (26 mg, 0.028 mmol), [(t-Bu)3PH]BF4 (16 mg, 0.056 mmol), and N,N-dicyclohexylmethylamine (433 μL, 2.04 mmol) in anhydrous 1,4-dioxane (6 mL) was heated at 95° C. overnight. The reaction was cooled to room temperature and filtered. The solvent was concentrated. The crude product was purified by silica chromatography to give ethyl 6-(3-cyanoprop-1-enyl)imidazo[1,2-a]pyridine-3-carboxylate (24v). MS m/z 256.4 (M+1)+. The reaction was cooled to room temperature filtered The solvent was concentrated The crude product was purified by silica chromatography

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (γ-Cyanopropyl) phenyldichlorosilane was prepared by adding 67.1 grams (1.0 moles) of allylcyanide slowly to 177.1 grams (1.0 moles) of phenyldichlorosilane containing 10-4 moles of platinum as chloroplatinic acid at a temperature of 130° - 135° C. in a three-necked flask. After completion of the addition, the reaction mixture was heated at 120° C. for 16 hours. The pure (γ-cyanopropyl) phenyldichlorosilane was isolated by fractional distillation (b.p. 132° C./0.7 mm). (γ-Cyanopropyl) phenyldichlorosilane was prepared After completion of the addition

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (γ-Cyanopropyl) phenyldichlorosilane was prepared by adding 67.1 grams (1.0 moles) of allylcyanide slowly to 177.1 grams (1.0 moles) of phenyldichlorosilane containing 10-4 moles of platinum as chloroplatinic acid at a temperature of 130° - 135° C. in a three-necked flask. After completion of the addition, the reaction mixture was heated at 120° C. for 16 hours. The pure (γ-cyanopropyl) phenyldichlorosilane was isolated by fractional distillation (b.p. 132° C./0.7 mm). (γ-Cyanopropyl) phenyldichlorosilane was prepared After completion of the addition