Reaction Steps
A solution of 9-fluorophenazine-1-carboxylic acid [Rewcastle et al., J. Synth Comm, 1987, 17, 1171] (200 mg, 0.8 mmol) in Me2NH (40% aqueous, 20 mL) was heated at 100° C. in a bomb for 3 h. The resulting intensely purple solution was diluted with water and then neutralized with AcOH. The aqueous solution was then extracted with CHCl3 (3×50 mL) until all color was extracted. The organic layer was further washed with water (1×150 mL), then dried over Na2SO4 and the solvent removed under reduced pressure. The resulting purple solid was dissolved in a minimal amount of CH2Cl2, and peteoleum ether was added until crystallization occurred, giving 9-(dimethylamino)phenazine-1-carboxylic acid as dark purple needles (210 g, 95%), mp 186-187.5° C. 1H NMR (CDCl3) δ 3.16 [s, 6 H, N(CH3)2 ], 7.26 (dd, J=6.8, 1.8 Hz, 1 H, H-6 or H-8), 7.81-7.88 (m, 2 H, H-7 and H-8 or H-6), 8.01 (dd, J=8.7, 7.0 Hz, 1 H, H-3), 8.48 (dd, J=8.7, 1.2 Hz, 1 H, H-4) and 8..91 (dd, J=7.0, 1.3 Hz, 1 H, H-2). Anal. (C15H13N3O2) C, H, N. Activation and coupling of this as above gave bis[((9-dimethylamino)phenazine-1-carboxamido)propyl]methylamine (54) as a red-purple oil (78%). 1H NMR (CDCl3) δ 1.91-2.00 (m, 4 H, 2×CH2CH2CH2), 2.29 (s, 3 H, NCH3), 2.57 (t, J=7.3 Hz, 4 H, CH2NCH3), 3.05 (s, 12 H, 2×N(CH3)2, 3.68 (q, J=6.5 Hz, 2 H, CH2NH), 7.07 (dd, J t 7.2, 1.3 Hz, 2 H, H-6 or H-8), 7.65 (dd, J=8.7, 7.3 Hz, 2 H, H-7), 7.70 (dd, J=8.7, 1.3 Hz, 2 H, H-8 or H-6), 7.90 (dd, J=8.6, 7.1 Hz, 2 H, H-3), 8.27 (dd, J=8.6, 1.4 Hz, 2 H, H-4), 8.87 (dd, J=7.1, 1.4 Hz, 2 H, H-2) and 10.99 (br t, J=5.1 Hz, 2 H, 2×CONH); HRMS (FAB+) m/z calcd for C37H42N9O2 644.3461 (MH+), found 644.3485.
