Reaction Steps
Oxidation to Example 3 Dess-Martin periodinane (1.83 g, 4.30 mmol) was added to a stirred solution of N—((S)-1-((3R,3aR,6aR)-3-hydroxydihydro-2H-furo[3,2-b]pyrrol-4(5H,6H, 6aH)-yl)-4-methyl-1-oxopentan-2-yl)-4-(4-propylpiperazin-1-yl)benzamide (250 mg, 0.546 mmol) in dichloromethane (45 mL) under an atmosphere of argon. The mixture was stirred for 18.5 hours then diluted with dichloromethane (200 mL). The organic phase was washed with aqueous sodium hydroxide solution (1M, 70 mL) then the aqueous extracted with dichloromethane (75 mL). The organic layer was washed with aqueous sodium hydroxide solution (1M, 70 mL) then brine (70 mL), then dried (Na2SO4), filtered and reduced in vacuo to give Example 3 as a pale yellow solid (0.831 g, 82%). TLC (Rf=0.30, MeOH:CH2Cl2 1:9), analytical HPLC main peak, Rt=9.80 min., HPLC-MS 471.3 [M+H]+, 489.3 [M+H2O+H]+, 963.6 [2M+Na]+; [α]D21−92.8° (c=3.29, CHCl3); δH (500 MHz, CDCl3)-hydrate not assigned here 0.91 (3H, d, J=6.58 Hz, CH(CH3)2), 0.93 (3H, t, J=7.32 Hz, CH2CH3), 1.00 (3H, d, J=6.47 Hz, CH(CH3)2), 1.52-1.78 (5H, m, CH2CH(CH3)2 and CH2CH3), 2.06-2.15 (1H, m, NCH2CH2CH), 2.29 (1H, dd, J=13.69 and 6.09 Hz, NCH2CH2CH), 2.40-2.45 (2H, m, NCH2CH2CH3), 2.66 (4H, brt, J=4.80 Hz, CH2NCH2CH2CH3), 3.35 (4H, brt, J=5.01 Hz, CH2CH2NCH2CH2CH3), 3.55-3.62 (1H, m, NCH2CH2CH), 3.98 (1H, d, J=17.03 Hz, OCH2C═O), 4.14 (1H, d, J=16.96 Hz, OCH2C═O), 4.17 (1H, brt, J=8.89 Hz, NCH2CH2CH), 4.66 (1H, d, J=5.16 Hz, NCH2CH2CHCH), 4.89 (1H, t, J=4.35 Hz, NCH2CH2CHCH), 5.01-5.06 (1H, m, CHCH2CH(CH3)2), 6.79 (1H, d, J=8.45 Hz, NH), 6.87 (2H, brd, J=8.97 Hz, aromatic CH), 7.70 (2H, brd, J=8.94 Hz, aromatic CH); δC (125 MHz, CDCl3) 11.91 (CH2CH3), 19.95 (CH2CH3), 22.12/23.28 and 24.77 (CH(CH3)2), 32.48 (NCH2CH2CH), 42.67 (CH2CH(CH3)2), 45.60 (NCH2CH2CHCH), 47.72 (NCH2CH2NCH2CH2CH3), 49.52 (CHCH2CH(CH3)2), 52.89 (NCH2CH2NCH2CH2CH3), 60.58 (NCH2CH2CH3), 62.15 (NCH2CH2CHCH), 71.02 (OCH2C═O), 80.78 (NCH2CH2CHCH), 114.06/114.09/128.51 and 128.59 (aromatic CH), 123.26 (aromatic quaternary), 153.49 (aromatic quaternary), 166.78 (NHC═O), 172.41 (CH2NC═O), 208.43 (ketone C═O).
