naphthalene-1,2-diamine

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1″,5″-[Bis-(4′-O-demethyl-4β-N-4-desoxypodophyllotoxin)] naphthalene diamine (4b) was prepared according to the method described earlier, employing 1,5-diamino naphthalene (80 mg, 0.5 mmol), Bu4N30I−(185 mg, 0.5 mmol), Et3N (150 mg, 1.5 mmol) and 4′-O-demethyl-4β-bromo-4-desoxy podophyllotoxin (462 mg, 1.0 mmol) to give the product in 76% yield. Spectral data: 1H NMR (CDCl3); 7.22-7.28 (d, 2H), 7.10-7.19 (t, 2H), 6.73 (S, 2H), 6.58 (S, 2H), 6.50 6.55 (d, 2H), 6.33 (S, 4H), 5.98 (ABq, 4H), 5.34 (S, 2H), 4.87 (br, 2H), 4.63-4.70 (d, 2H), 4.52-4.59 (d, 2H), 4.36-4.48 (t, 2H), 3.85-3.95 (d, 2H), 3.82 (3, 6H), 3.20-3.31(dd, 2H), 2.98-3.16 (m, 2H); FAB MS: m/z 922 (M+); mp. 238-240° C. to give the product in 76% yield

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7.38 g of 1,2-diaminonaphthalene in 175 ml of ethanol was added 8.56 ml of triethyl orthoacetate and the reaction mixture heated to reflux for 3.5 hours. The solvent was removed in vacuo and the residue partitioned between chloroform and water. The organic phase was separated, dried over magnesium sulfate and concentrated to a dark oil, 9.0 g. the reaction mixture heated to reflux for 3.5 hours The solvent was removed in vacuo the residue partitioned between chloroform and water The organic phase was separated dried over magnesium sulfate concentrated to a dark oil, 9.0 g

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Oxo-1,2,3,5-tetrahydronaphtho[2′,1′:4,5]imidazo[1,2-a]pyridine-4-carboxylic acid ethyl ester (X) In a manner similar to the conversion of III to IV, compound IX (1.75 g, 4.94 mmol) was converted to X, 1.18 g (78%): MS m/z 309 (MH+); 1H NMR (DMSO-d6) δ 1.27 (t, 3H), 2.69 (t, 2H), 4.22 (q, 2H), 4.85 (t, 2H), 7.53 (dd, 1H), 7.64 (dd, 1H), 7.82 (d, 1H), 7.87 (d, 1H), 8.06 (d, 1H), 8.49 (d, 1H) and 12.64 (br s, 1H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of VII (11.4 g, 58 mmol) and ethyl 3-bromopropionate (7.5 mL, 58 mmol) in DMF (120 mL) was heated to 50° C. for 8 h. The reaction mixture was poured into water and neutralized with NaHCO3. The products were extracted into CH2Cl2 (2×200 mL). The combined organics were washed with water (4×200 mL) and dried over Na2SO4. The solvent was evaporated in vacuo and the products separated by flash chromatography using 27% EtOAc in hexane as the eluant to give the product VIII, 2.60 g (17%) as a brown solid: MS m/z 259 (MH+); 1H NMR (DMSO-d6) δ 1.22 (t, 3H), 2.64 (t, 2H), 3.09 (br t, 2H), 4.05 (br s, 1H), 4.09 (q, 2H), 5.19 (br s, 2H), 7.04 (d, 1H), 7.13 (dd, 1H), 7.33 (dd, 1H), 7.40 (d, 1H), 7.66 (d, 1H) and 7.97 (d, 1H); and the product XII, 2.06 g (13%) as a brown solid: MS m/z 259 (MH+); H NMR (DMSO-d6) d 1.21 (t, 3H), 2.63 (t, 2H), 3.43 (br m, 2H), 4.10 (q, 2H), 4.65 (br s, 1H), 4.97 (br s, 2H), 7.04 (d, 1H), 7.11-7.18 (m, 2H), 7.27 (dd, 1H), 7.62 (d, 1H), and 7.94 (d, 1H) The products were extracted into CH2Cl2 (2×200 mL) The combined organics were washed with water (4×200 mL) dried over Na2SO4 The solvent was evaporated in vacuo the products separated by flash chromatography