Triphosgene → Bis(2-chloroethyl)-4-isocyanatophenylamine

To a suspension of N,N-bis(2-chloroethyl)benzene-1,4-diamine hydrochloride (18, 0.826 g, 2.7 mmol) in dry CHCl3 (10 mL), Et3N (1.5 mL) was added dropwise at −5-0° C. The resulting solution was added dropwise to a solution of triphosgene (0.296 g, 1 mmol) in dry CHCl3 (10 mL) at −5-0° C. The reaction mixture was stirred at room temperature for 30 min. The resulting solution was evaporated under reduced pressure to dryness to give crude isocyanate (19) as liquid. This solution was added dropwise into a suspension of known 4-hydrazino-6-methoxy-2-methylquinoline (0.36 g, 1.5 mmol)55 and Et3N (2 mL) in dry DMF (15 mL at 0° C. The reacting mixture was stirred at room temperature for 1.5 h. The resulting solution was evaporated under reduced pressure to dryness. The solid residue was triturated with a mixture of THF/ether (2:1 v/v) and the solid was collected by filtration, washed with little amount of cold chloroform and methanol, and dried to give N-{4-[bis(2-chloroethyl)amino]phenyl}-2-(6-methoxy-2-methyl-4-quinolinyl)hydrazinecarboxamide (BO-1228), 0.413 g (60%): mp 224-225° C.; 1H NMR (DMSO-d6) δ 2.68 (3H, s, Me), 3.68-3.70 (8H, m, 4×CH2), 3.94 (3H, s, OMe), 6.70 (2H, d, J=9.0 Hz, ArH), 6.84 (1H, s, ArH), 7.31 (2H, d, J=9.0 Hz, ArH), 7.61 (1H, dd, J=2.2 and 9.2 Hz, ArH), 7.91 (1H, d, J=2.2 Hz, ArH), 7.96 (1H, d, J=9.2 Hz, ArH), 9.01 and 9.11 (each 1H, s, exchangeable, 2×NH), 10.65 (1H, brs, exchangeable, NH). Anal. Calcld. for (C22H25Cl2N5O2): C, 57.14; H, 5.45; N, 15.15. Found: C, 57.40; H, 5.18; N, 15.52.

1. additionwas added dropwise at −5-0° C
2. customThe resulting solution was evaporated under reduced pressure to dryness

ORD record

ord-c382a60007154d0ba2c7183e7e0b5e41

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193687B2