p-Toluenesulfonic acid → N-(2,6-difluorophenyl)-3-[3-(2-{[2-(methyloxy)-4-(4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}-1-piperidinyl)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamide

HRID 419371Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:17]2[CH:18]=[C:19]([CH:31]=[CH:32][CH:33]=2)[C:20]([NH:22][C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])=[O:21])[CH:5]=[CH:4][N:3]=1.[CH3:34][O:35][C:36]1[CH:42]=[C:41]([N:43]2[CH2:48][CH2:47][CH:46]([N:49]3[CH2:54][CH2:53][N:52]([CH2:55][CH2:56][S:57]([CH3:60])(=[O:59])=[O:58])[CH2:51][CH2:50]3)[CH2:45][CH2:44]2)[CH:40]=[CH:39][C:37]=1[NH2:38].C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)C>[F:30][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([F:29])[C:23]=1[NH:22][C:20](=[O:21])[C:19]1[CH:31]=[CH:32][CH:33]=[C:17]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:38][C:37]3[CH:39]=[CH:40][C:41]([N:43]4[CH2:44][CH2:45][CH:46]([N:49]5[CH2:50][CH2:51][N:52]([CH2:55][CH2:56][S:57]([CH3:60])(=[O:59])=[O:58])[CH2:53][CH2:54]5)[CH2:47][CH2:48]4)=[CH:42][C:36]=3[O:35][CH3:34])[N:7]=2)[CH:18]=1

Participants

Conditions

Temperature: 175 °C

Procedure

A mixture of 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (0.70 g, 1.52 mmol), 2-(methyloxy)-4-(4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}-1-piperidinyl)aniline (0.60 g, 1.52 mmol), p-toluenesulfonic acid (0.69 g, 3.64 mmol) and iPrOH (15 mL) were heated in the microwave at 175° C. for 25 min. LCMS indicated the reaction had proceeded to completion and the reaction mixture was concentrated onto silica gel. Flash chromatography afforded the title compound (0.80 g, 64%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 10.23 (s, 1H), 9.40 (bs, 1H), 8.45 (s, 1H), 8.33-8.31 (m, 1H), 8.19 (d, J=5.5 Hz, 1H), 8.07-8.03 (m, 1H), 7.83-7.79 (m, 1H), 7.74-7.70 (m, 1H), 7.60 (at, J=7.9 Hz, 1H), 7.48-7.35 (m, 3H), 7.24-7.16 (m, 2H), 7.00-6.94 (m, 1H), 6.67 (d, J=2.2 Hz, 1H), 6.50-6.44 (m, 2H), 3.79 (s, 3H), 3.75-3.68 (m, 2H), 3.25 (t, J=6.6 Hz, 2H), 3.01 (s, 3H), 2.70-2.60 (m, 5H), 2.45-2.24 (m, 5H), 1.86-1.79 (m, 2H), 1.55-1.44 (m, 2H). MS (ES+, m/z) 822 (M+1).

Workup

concentrationthe reaction mixture was concentrated onto silica gel

Sources & evidence

ORD record: ord-8681704682d8494c8464a3d52cb75438
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093239B2

Reaction notes

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