4-methylpentanenitrile

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

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

Procedure: This compound was synthesized in an analogous manner to Example 32 but using 4-methylpentanenitrile (commercially available from TCI America Organic Chemicals Order Number M0458) instead of acetonitrile in the preparation of allyl 4-isobutyl-3-(isoquinolin-6-yl)isoxazol-5-ylcarbamate according to Scheme 6 instead of allyl 3-(isoquinolin-6-yl)isoxazol-5-ylcarbamate. MS m/z: 440 (M+1); 1H NMR (400 MHz, CD3OD) δ ppm 9.73 (s, 1H), 8.61 (d, J=6.65 Hz, 1H), 8.53-8.57 (m, 1H), 8.43 (s, 2H), 8.15 (dd, J=8.61, 1.56 Hz, 1H), 0.57 (d, J=7.43 Hz, 1H), 7.40 (d, J=8.22 Hz, 1H), 7.25 (s, 1H), 7.15 (t, J=7.43 Hz, 1H), 7.06 (t, J=7.24 Hz, 1H), 3.78-3.83 (m, 1H), 3.63-3.68 (m, 2H), 3.22-3.28 (m, 1H), 3.10-3.16 (m, 1H), 2.37 (d, J=7.43 Hz, 2H), 1.58 (dt, J=13.60, 6.70 Hz, 1H), 0.76 (d, J=6.65 Hz, 6H). This compound was synthesized in an analogous manner to Example 32

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

Procedure: This compound was synthesized in an analogous manner to Example 32 but using 4-methylpentanenitrile (commercially available from TCI America Organic Chemicals Order Number M0458) instead of acetonitrile in the preparation of allyl 4-isobutyl-3-(isoquinolin-6-yl)isoxazol-5-ylcarbamate according to Scheme 6 instead of allyl 3-(isoquinolin-6-yl)isoxazol-5-ylcarbamate. MS m/z: 440 (M+1); 1H NMR (400 MHz, CD3OD) δ ppm 9.73 (s, 1H), 8.61 (d, J=6.65 Hz, 1H), 8.53-8.57 (m, 1H), 8.43 (s, 2H), 8.15 (dd, J=8.61, 1.56 Hz, 1H), 0.57 (d, J=7.43 Hz, 1H), 7.40 (d, J=8.22 Hz, 1H), 7.25 (s, 1H), 7.15 (t, J=7.43 Hz, 1H), 7.06 (t, J=7.24 Hz, 1H), 3.78-3.83 (m, 1H), 3.63-3.68 (m, 2H), 3.22-3.28 (m, 1H), 3.10-3.16 (m, 1H), 2.37 (d, J=7.43 Hz, 2H), 1.58 (dt, J=13.60, 6.70 Hz, 1H), 0.76 (d, J=6.65 Hz, 6H). This compound was synthesized in an analogous manner to Example 32

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

Procedure: A mixture of isocapronitrile (1.00 g, 10.30 mmol), hydroxylamine hydrochloride (0.786 g, 11.32 mmol), and sodium hydroxide (0.453 g, 11.32 mmol) in EtOH (21 mL) and water (5 mL) was stirred at room temperature for 48 hours. The reaction mixture was concentrated in vacuo to yield a white solid which was re-dissolved in dichloromethane (100 mL). The insoluble salt was removed by filtration. The organic layer was concentrated in vacuo to dryness. The title compound was obtained as a white solid in 55% yield (0.730 g). 1H NMR (300 MHz, CDCl3) δ 6.6 (br., s, 1H), 4.5 (br., s, 2H), 2.2 (m, 2H), 1.50 (m, 1H), 1.4 (m, 2H), 0.85 (m, 6H). The reaction mixture was concentrated in vacuo to yield a white solid which The insoluble salt was removed by filtration The organic layer was concentrated in vacuo to dryness

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

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of about 50.g grams (0.515 mole) isoamyl cyanide, about 31.5 grams (0.515 mole) ethanolamine, and about 3.2 grams (0.012 mole) cadmium acetate dihydrate is heated to about 115 degrees C. to about 125 degrees C. and stirred under nitrogen for about two days. The product is distilled under vacuum and the fraction boiling at about 81 degrees C. to about 84 degrees C. at about 29 mmHg is collected. to about 125 degrees C The product is distilled under vacuum to about 84 degrees C at about 29 mmHg is collected

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

Procedure: This compound was synthesized in an analogous manner to Example 32 but using 4-methylpentanenitrile (commercially available from TCI America Organic Chemicals Order Number M0458) instead of acetonitrile in the preparation of allyl 4-isobutyl-3-(isoquinolin-6-yl)isoxazol-5-ylcarbamate according to Scheme 6 instead of allyl 3-(isoquinolin-6-yl)isoxazol-5-ylcarbamate. MS m/z: 440 (M+1); 1H NMR (400 MHz, CD3OD) δ ppm 9.73 (s, 1H), 8.61 (d, J=6.65 Hz, 1H), 8.53-8.57 (m, 1H), 8.43 (s, 2H), 8.15 (dd, J=8.61, 1.56 Hz, 1H), 0.57 (d, J=7.43 Hz, 1H), 7.40 (d, J=8.22 Hz, 1H), 7.25 (s, 1H), 7.15 (t, J=7.43 Hz, 1H), 7.06 (t, J=7.24 Hz, 1H), 3.78-3.83 (m, 1H), 3.63-3.68 (m, 2H), 3.22-3.28 (m, 1H), 3.10-3.16 (m, 1H), 2.37 (d, J=7.43 Hz, 2H), 1.58 (dt, J=13.60, 6.70 Hz, 1H), 0.76 (d, J=6.65 Hz, 6H). This compound was synthesized in an analogous manner to Example 32

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

Procedure: A mixture of isocapronitrile (1.00 g, 10.30 mmol), hydroxylamine hydrochloride (0.786 g, 11.32 mmol), and sodium hydroxide (0.453 g, 11.32 mmol) in EtOH (21 mL) and water (5 mL) was stirred at room temperature for 48 hours. The reaction mixture was concentrated in vacuo to yield a white solid which was re-dissolved in dichloromethane (100 mL). The insoluble salt was removed by filtration. The organic layer was concentrated in vacuo to dryness. The title compound was obtained as a white solid in 55% yield (0.730 g). 1H NMR (300 MHz, CDCl3) δ 6.6 (br., s, 1H), 4.5 (br., s, 2H), 2.2 (m, 2H), 1.50 (m, 1H), 1.4 (m, 2H), 0.85 (m, 6H). The reaction mixture was concentrated in vacuo to yield a white solid which The insoluble salt was removed by filtration The organic layer was concentrated in vacuo to dryness

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