| 46% |
|
To a vigorously stirred suspension of (iodomethyl)triphenylphosphonium iodide (1.3 g, 2.4 mmol) in dry THF (18 mL) under nitrogen, was added sodium bis(trimethylsilyl)amide (2.4 mL, 1 M in THF, 2.4 mmol). After 10 min at room temperature, the mixture was cooled to 0 C. and acetyl cyclosporin aldehyde from Example 2 (300 mg, 0.240 mmol) in anhydrous THF (10 mL) was added dropwise. After 10 min at 0 C., the reaction was quenched with a saturated solution of ammonium chloride (10 mL), and then allowed to warm to room temperature. The resulting solid was filtered off through a plug of diatomaceous earth and washed with ethyl acetate (200 mL). The organic layer was washed with an aqueous solution of sodium hydrogensulfite (20%, 200 mL), then dried over anhydrous sodium sulfate and concentrated under vacuum to afford the crude product (540 mg). The material was purified by semi-preparative HPLC to afford the acetate of the cis-isomer of cyclosporin vinyl iodide (150 mg, 46%) as a pale-brown oil: 1H NMR (300 MHz, CDCl3) δ 8.53 (d, J=9.8 Hz, 1H), 8.15 (d, J=6.5 Hz, 1H), 7.82 (d, J=9.0 Hz, 1H), 7.63 (d, J=8.2 Hz, 1H), 6.10 (d, J=7.4 Hz, 1H), 6.02-5.94 (m, 1H), 5.69 (dd, J=10.9, 3.8 Hz, 1H), 5.61-5.48 (m, 2H), 5.38-5.13 (m, 3H), 4.98 (d, J=10.9 Hz, 2H), 4.87 (t, J=7.4 Hz, 1H), 4.78 (t, J=9.6 Hz, 1H), 4.63 (d, J=14.2 Hz, 1H), 4.47 (t, J=7.0 Hz, 1H), 3.98 (s, 3H), 3.43 (s, 3H), 3.27 (s, 3H), 3.21 (s, 3H), 3.19 (s, 3H), 3.14 (s, 3H), 2.69 (s, 3H), 2.42-2.30 (m, 1H), 2.22-1.85 (m, 8H), 2.06 (s, 3H), 1.77-1.60 (m, 3H), 1.54-0.75 (m, 56H); ESI MS m/z 1357 [C63H110IN11O13+H]+. |
| 46% |
|
To a vigorously stirred suspension of (iodomethyl)triphenylphosphonium iodide (1.3 g, 2.4 mmol) in dry THF (18 mL) under nitrogen, was added sodium bis(trimethylsilyl)amide (2.4 mL, 1 M in THF, 2.4 mmol). After 10 min at room temperature, the mixture was cooled to 0 C. and acetyl cyclosporin aldehyde from Example 2 (300 mg, 0.240 mmol) in anhydrous THF (10 mL) was added dropwise. After 10 min at 0 C., the reaction was quenched with a saturated solution of ammonium chloride (10 mL), and then allowed to warm to room temperature. The resulting solid was filtered off through a plug of diatomaceous earth and washed with ethyl acetate (200 mL). The organic layer was washed with an aqueous solution of sodium hydrogensulfite (20%, 200 mL), then dried over anhydrous sodium sulfate and concentrated under vacuum to afford crude product (540 mg). The material was purified by semi-preparative HPLC to afford the acetate of the cis-isomer of cyclosporin vinyl iodide (150 mg, 46%) as a pale-brown oil: 1H NMR (300 MHz, CDCl3) δ 8.53 (d, J=9.8 Hz, 1H), 8.15 (d, J=6.5 Hz, 1H), 7.82 (d, J=9.0 Hz, 1H), 7.63 (d, J=8.2 Hz, 1H), 6.10 (d, J=7.4 Hz, 1H), 6.02-5.94 (m, 1H), 5.69 (dd, J=10.9, 3.8 Hz, 1H), 5.61-5.48 (m, 2H), 5.38-5.13 (m, 3H), 4.98 (d, J=10.9 Hz, 2H), 4.87 (t, J=7.4 Hz, 1H), 4.78 (t, J=9.6 Hz, 1H), 4.63 (d, J=14.2 Hz, 1H), 4.47 (t, J=7.0 Hz, 1H), 3.98 (s, 3H), 3.43 (s, 3H), 3.27 (s, 3H), 3.21 (s, 3H), 3.19 (s, 3H), 3.14 (s, 3H), 2.69 (s, 3H), 2.42-2.30 (m, 1H), 2.22-1.85 (m, 8H), 2.06 (s, 3H), 1.77-1.60 (m, 3H), 1.54-0.75 (m, 56H); ESI MS m/z 1357 [C63H110IN11O13+H]+. |
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