p-Toluenesulfonic acid → N-(2,6-difluorophenyl)-3-(3-(2-(2-methoxy-4-(4-(4-(methylsulfonyl)piperazin-1-yl)piperidin-1-yl)phenylamino)pyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)benzamide

HRID 419368Notes

Reaction equation

HRID 419368 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]([S:55]([CH3:58])(=[O:57])=[O:56])[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[CH2:48][CH2:47][CH:46]([N:49]5[CH2:54][CH2:53][N:52]([S:55]([CH3:58])(=[O:57])=[O:56])[CH2:51][CH2:50]5)[CH2:45][CH2:44]4)=[CH:42][C:36]=3[O:35][CH3:34])[N:7]=2)[CH:18]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 574161512-(Methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}anilineHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

Product 1

HCID 25124150N-(2,6-difluorophenyl)-3-(3-(2-(2-methoxy-4-(4-(4-(methylsulfonyl)piperazin-1-yl)piperidin-1-yl)phenylamino)pyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)benzamideYield 65%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

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) (1.00 g, 2.2 mmol), 2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}aniline (0.80 g, 2.2 mmol), p-toluenesulfonic acid (0.99 g, 5.2 mmol) and iPrOH (20 mL) was heated in the microwave at 175° C. for 20 min. LCMS indicated the reaction had proceeded to completion and the reaction mixture was concentrated onto silica gel. Flash chromatography afforded the title compound (1.1 μg, 65%) 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=5.2 Hz, 1H), 8.07-8.03 (m, 1H), 7.83-7.80 (m, 1H), 7.74-7.71 (m, 1H), 7.60 (at, J=7.7 Hz, 1H), 7.48-7.35 (m, 3H), 7.23-7.17 (m, 2H), 7.01-6.95 (m, 1H), 6.67 (d, J=2.5 Hz, 1H), 6.50-6.44 (m, 2H), 3.79 (s, 3H), 3.76-3.70 (m, 2H), 3.11-3.06 (m, 4H), 2.85 (s, 3H), 2.71-2.63 (m, 2H), 2.62-2.57 (m, 4H), 2.46-2.36 (m, 2H), 1.87-1.79 (m, 2H), 1.60-1.47 (m, 2H). MS (ES+, m/z) 794 (M+1).

Workup

  1. concentrationthe reaction mixture was concentrated onto silica gel

Sources & evidence

ORD record
ord-c251ef7b95b3452992c710331bddacd0
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

Loading…