Reaction Steps
Dess-Martin periodinane (2.82 g, 6.66 mmol) was added to a stirred solution of N—((S)-1-((3R,3aR,6R,6aS)-3-hydroxy-6-methoxydihydro-2H-furo[3,2-b]pyrrol-4(5H,6H,6aH)-yl)-4,4-dimethyl-1-oxopentan-2-yl)-4-(4-isopropylpiperazin-1yl)benzamide (1.72 g, 3.33 mmol) in dichloromethane (65 mL) under an atmosphere of argon. The mixture was stirred for 18 hours then diluted with dichloromethane (300 mL). The organic phase was washed with aqueous sodium hydroxide solution (1M, 100 mL) then the aqueous extracted with dichloromethane (150 mL). The organic layer was washed with aqueous sodium hydroxide solution (1M, 100 mL) then brine (150 mL), then dried (Na2SO4), filtered and reduced in vacuo to give 4-(4-isopropylpiperazin-1-yl)-N—((S)-1-((3aS,6R,6aS)-6-methoxy-3-oxodihydro-2H-furo[3,2-b]pyrrol-4(5H,6H,6aH)-yl)-4,4-dimethyl-1-oxopentan-2-yl)benzamide a pale yellow solid (1.408 g, 82%). TLC (Rf=0.45, MeOH:CH2Cl2 1:19), analytical HPLC main peak, Rt=10.39 min., HPLC-MS 515.3 [M+H]+, 533.3 [M+H2O+H]+, 1051.6 [2M+Na]+; [□]D22−31.08° (c=3.7, CHCl3); δH (500 MHz, CDCl3) 0.99 (9H, s, C(CH3)3), 1.08 (6H, d, J=6.52 Hz, NCH(CH3)2), 1.68-1.74 (2H, m, CH2C(CH3)3), 2.65 (4H, brt, J=5.04 Hz, CH2NCH(CH3)2), 2.67-2.73 (1H, m, NCH(CH3)2), 3.29 (4H, brt, J=5.05 Hz, CH2CH2NCH(CH3)2), 3.49 (3H, s, OCH3), 3.61 (1H, dd, 5.35 Hz, NCH2CHOCH3), 4.00-4.04 (1H, m, CHOCH3), 4.09 (1H, d, J=16.89 Hz, OCH2C═O), 4.20 (1H, d, J=16.93 Hz, OCH2C═O), 4.27 (1H, dd, 5.88 Hz, NCH2CHOCH3), 4.74 (1H, d, J=6.86 Hz, OCH2(C═O)CH), 4.91 (1H, dd, 4.28 Hz, OCHCHOCH3), 4.94-5.00 (1H, m, CHCH2C(CH3)3), 6.61 (1H, d, J=8.69 Hz, NH), 6.84 (2H, brd, J=8.95 Hz, aromatic CH), 7.65 (2H, brd, J=8.91 Hz, aromatic CH); δC (125 MHz, CDCl3) 18.53 (NCH(CH3)2), 29.75/29.80 (C(CH3)3), 30.75/30.77 (C(CH3)3), 46.53 (CH2C(CH3)3), 47.02 (NCH2CH2NCH(CH3)2), 48.24 (CHCH2C(CH3)3), 48.43 (NCH2CH2NCH(CH3)2), 49.76 (NCH2CHOCH3), 54.49 (NCH(CH3)2), 58.23 (OCH3), 60.49 (OCH2C(═O)CH), 71.45 (OCH2C═O), 78.84 (CHOCH3), 80.25 (OCHCHOCH3), 114.01/114.10/128.49 and 129.83 (aromatic CH), 123.08 (aromatic quaternary), 153.55 (aromatic quaternary), 166.69 (NHC═O), 173.53 (CH2NC═O), 207.93 (ketone C═O).
