Methyl iodide → CERATAMINE A

Participants

Reaction Conditions

Reaction Steps

Sodium bis(trimethylsilyl)amide (1 M in THF, 24 μL, 0.0240 mmol) was added dropwise to a solution of ceratamine B from Example 12 (formula (IIIB); R1=methyl) (12.1 mg, 0.0266 mmol) in DMF:THF (1:1, 0.27 mL) at 0° C. The reaction mixture was cooled to −78° C. and iodomethane (2.1 μL, 0.0346 mmol) was added dropwise followed by warming to −10° C. The reaction was quenched by the addition H2O (2 mL), and was extracted with EtOAc (6×5 mL). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo to afford crude ceratamine A (formula (IIIA); R1=methyl). Purification by flash chromatography (C-18 reverse-phase silica, 70% MeOH:H2O) yielded pure ceratamine A (formula (IIIA); R1=methyl) (5.4 mg, 0.0116 mmol, 43%) as a yellow solid. The major tautomer was characterized: 1H NMR (400 MHz, DMSO) δ 8.68 (m, NH), 7.74 (d, J=9.9 Hz, 1H), 7.66 (s, 2H), 6.42 (d, J=9.9 Hz, 1H), 4.23 (s, 2H), 3.72 (s, 3H), 3.55 (s, 3H), 3.07 (d, J=4.9 Hz, 3H); 13C NMR (100 MHz, DMSO) δ 175.6, 169.7, 164.1, 160.5, 151.4, 142.9, 140.2, 133.1, 121.3, 116.6, 100.4, 60.3, 43.7, 35.0, 29.2; HRMS (ESI) m/z calcd for C17H17Br2N4O2: 466.9713. found: 466.9701. These data from synthetic ceratamine A are consistent with data reported for natural products.

Provenance & Evidence