p-Toluenesulfonic acid monohydrate → N-(4-Fluoro-2-methoxy-5-nitrophenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-amine

HRID 1842782Notes

Reaction equation

O.C1(C)C=CC(S(O)(=O)=O)=CC=1.Cl[C:14]1[N:19]=[C:18]([C:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]([CH3:29])[CH:21]=2)[CH:17]=[CH:16][N:15]=1.[F:30][C:31]1[C:37]([N+:38]([O-:40])=[O:39])=[CH:36][C:34]([NH2:35])=[C:33]([O:41][CH3:42])[CH:32]=1>CC(O)CCC>[F:30][C:31]1[C:37]([N+:38]([O-:40])=[O:39])=[CH:36][C:34]([NH:35][C:14]2[N:19]=[C:18]([C:20]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]([CH3:29])[CH:21]=3)[CH:17]=[CH:16][N:15]=2)=[C:33]([O:41][CH3:42])[CH:32]=1

Participants

Conditions

Temperature: 105 °C

Procedure

p-Toluenesulfonic acid hydrate (22.73 g, 119.5 mmol) was added in one portion to a mixture of 3-(2-chloropyrimidin-4-yl)-1-methylindole (Intermediate 130, 24.27 g, 99.58 mmol) and 4-fluoro-2-methoxy-5-nitroaniline (Intermediate 23, 18.54 g, 99.58 mmol) in 2-pentanol (500 mL). The resulting mixture was stirred at 105° C. for 2.5 h. and then cooled to r.t. The resulting precipitate was collected by filtration, washed with 2-pentanol (50 mL) and dried under vacuum to give some of the desired product as a yellow solid. The filtrate was cooled and the resulting precipitate was collected by filtration and washed with 2-pentanol (10 mL). The two crops of product were combined and triturated with CH3CN to give a solid which was collected by filtration and dried under vacuum to give the title compound (37.4 g, 95%) as a yellow solid; 1H NMR: 3.92 (3H, s), 4.01 (3H, s), 7.13 (1H, dd), 7.27-7.36 (1H, m), 7.40-7.51 (2H, m), 7.59 (1H, d), 8.26 (1H, t), 8.35 (1H, d), 8.61 (1H, s), 8.85 (1H, d), 9.46 (1H, s); m/z: ES− M− 392.

Workup

temperaturecooled to r.t
filtrationThe resulting precipitate was collected by filtration
washwashed with 2-pentanol (50 mL)
customdried under vacuum

Sources & evidence

ORD record: ord-b22d155d5842482db221a44171ad359a
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946235B2

Reaction notes

Loading…