Methanol → HCID 136355292, compound

General Procedure for the Synthesis of Sulfonamides (Scheme 4). 6,7-Bis-allyloxy-2-[4-(biphenyl-4-sulfonyl)-piperazin-1-yl]-quinazolin-4-ylamine (43): A solution of 4-amino-2-chloro-6,7-dimethoxyquinazoline (2.51 g, 10.0 mmol) in CH2Cl2 (30 mL) was cooled to −70° C. under argon, and added boron tribromide (6.01 g, 12.0 mmol). The mixture was allowed to warm up to room temperature over a period of 4 h, cooled to −70° C., added methanol (30 mL), and concentrated. The solid residue was washed with ethyl acetate to obtain 4-amino-2-chloro-6,7-dihydroxyquinazoline [1HNMR (DMSO-d6) δ 7.04 (s, 1 H), 7.51 (s, 1 H)]. A mixture of the first intermediate (0.21 g, 1.0 mmol), allyl bromide (0.432 g, 3.6 mmol) and K2CO3 (0.331 g, 2.4 mmol) in methanol (10 mL) was stirred under reflux for 12 h, concentrated, and purified by silica gel chromatography to afford 4-amino-2-chloro-6,7-diallyloxyquinazoline [1HNMR (DMSO-d6) δ 4.63 (d, J=5.4 Hz, 2 H), 4.70 (d, J=1.5 Hz, 2 H), 5.28 (d, J=1.3 Hz, 2 H), 5.42 (d, J=1.3 Hz, 1 H), 5.49 (d, J=1.3 Hz, 1 H), 6.07-6.11 (m, 2 H), 7.06 (s, 1 H), 7.62 (s, 1 H)]. A solution of the second intermediate (0.291 g, 1.0 mmol) and 1-(biphenyl-4-sulfonyl)piperazine (0.302 g, 1.0 mmol) in 1-butanol (5 mL) was stirred under reflux for 8 h, and concentrated. The solid residue was stirred with methanol under reflux for 30 min, filtered, washed with methanol to yield compound 44. 1HNMR (DMSO-d6) δ 3.36 (br s, 4 H), 4.01 (br s, 4 H), 4.60-4.64 (m, 4 H), 5.26-5.35 (m, 4 H), 6.02-6.13 (m, 2 H), 7.30-7.52 (m, 4 H), 7.72-7.75 (m, 3 H), 7.83-7.86 (m, 4 H), 8.63 (s, 1 H), 8.83 (s, 1H). HRMS (M+H)+ calcd for C30H32N5O4S 558.2169, found 558.2169. Anal. (C30H31N5O4S.HCl) C, H, N.

1. temperaturecooled to −70° C.
2. concentrationconcentrated
3. washThe solid residue was washed with ethyl acetate

ORD record

ord-5f8fe6ad23694b3ba1eaaa8374bc0e7a

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08377948B2