p-Toluenesulfonic acid → 4-[(4-Bromo-3-hydroxybenzyl)(4-cyanophenyl)amino]-4H-[1,2,4]triazole
Reaction equation
O1CCCCC1[O:7][C:8]1[CH:9]=[C:10]([CH:26]=[CH:27][C:28]=1[Br:29])[CH2:11][N:12]([C:18]1[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=1)[N:13]1[CH:17]=[N:16][N:15]=[CH:14]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Br:29][C:28]1[CH:27]=[CH:26][C:10]([CH2:11][N:12]([C:18]2[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=2)[N:13]2[CH:14]=[N:15][N:16]=[CH:17]2)=[CH:9][C:8]=1[OH:7]Participants
4
Procedure
The title compound was prepared by adapting the method reported by Tafi et al.[Tafi,2002] with the following modifications. To a solution of 4-[(3-(tetrahydropyran-2-yloxy)-4-bromobenzyl)(4-cyanophenyl)amino]-4H-[1,2,4]triazole (3.05 g, 6.71 mmol) in MeOH (60 mL) was added a catalytic amount of p-toluenesulfonic acid at 0° C. and the mixture was stirred (allowing to slowly warm to room temperature) overnight. The solvent was removed in vacuo and the residue dissolved in EtOAc (100 mL). The organic fraction was washed with Na2CO3 solution (1M aqueous solution, 3×50 mL), brine (3×50 mL) and dried (Na2SO4). The solvent was removed in vacuo and the pale yellow residue recrystallised from EtOH to give STX1216 as an off-white powder (1.48 g, 60%); δH (400 MHz, DMSO-d6) 5.00 (s, 2H), 6.72 (dd, J=8.3, 2.1, 1H), 6.76 (AA′BB′, 2H), 6.86 (d, J=1.8, 1H), 7.43 (d, J=8.0, 1H), 7.78 (AA′BB′, 2H), 8.81 (s, 2H), 10.32 (s, 1H—exchanges with D2O); δC (100 MHz, DMSO-d6) 57.08 (CH2), 103.32, 109.42 114.07 (2×CH), 116.66 (CH), 119.51 (CH), 120.90 (CH), 133.54 (2×CH), 134.45 (2×CH), 136.14, 143.90, 151.82, 154.60; LRMS (FAB+) m/z (rel. intensity) 372.1 (94, [C16H12N5O81Br+H], 370.1 (100, [C16H12N5O79Br+H]); LC-MS (ES−) TR=1.98 min, m/z 368.1 (C16H12N5O79Br—H), 370.1 (C16H12N5O81Br—H); HPLC tR=1.77 min (100%); HRMS (FAB+) Found 372.02789; C16H13N5O81Br requires 372.02830. Found: C, 51.6; H, 3.4; N, 18.9; C16H12N5OBr requires C, 51.9; H, 3.3; N, 18.9%.