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

HRID 419636Notes

Reaction equation

HRID 419636 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.[CH2:34]([O:36][C:37]1[CH:43]=[C:42]([N:44]2[CH2:49][CH2:48][CH:47]([N:50]3[CH2:55][CH2:54][N:53]([S:56]([CH3:59])(=[O:58])=[O:57])[CH2:52][CH2:51]3)[CH2:46][CH2:45]2)[CH:41]=[CH:40][C:38]=1[NH2:39])[CH3:35].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:39][C:38]3[CH:40]=[CH:41][C:42]([N:44]4[CH2:49][CH2:48][CH:47]([N:50]5[CH2:55][CH2:54][N:53]([S:56]([CH3:59])(=[O:58])=[O:57])[CH2:52][CH2:51]5)[CH2:46][CH2:45]4)=[CH:43][C:37]=3[O:36][CH2:34][CH3:35])[N:7]=2)[CH:18]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamideHCID 594529942-(Ethyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}aniline

Product 1

HCID 59452813N-(2,6-difluorophenyl)-3-(3-{2-[(2-(ethyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamideYield 63%

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) (0.10 g, 0.22 mmol), 2-(ethyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}aniline (Example 222, Step D) (0.083 g, 0.22 mmol) and para-toluenesulfonic acid (0.099 g, 0.52 mmol) in i-PrOH (5 mL) was heated in a microwave at 175° C. for 25 min. The reaction mixture was concentrated onto silica gel and purified by flash chromatography. Recrystallization from DCM and diethyl ether afforded N-(2,6-difluorophenyl)-3-(3-{2-[(2-(ethyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamide (0.110 g, 63%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.25 (s, 1H), 9.39 (br. s., 1H), 8.38 (s, 1H), 8.35 (s, 1H), 8.24 (d, J=5.2 Hz, 1H), 8.06 (d, J=7.9 Hz, 1H), 7.82 (d, J=7.8 Hz, 1H), 7.74 (d, J=9.0 Hz, 1H), 7.62 (t, J=7.7 Hz, 1H), 7.36-7.52 (m, 3H), 7.16-7.26 (m, 2H), 6.94-7.02 (m, 1H), 6.67 (d, J=2.2 Hz, 1H), 6.45-6.54 (m, 2H), 4.07 (q, J=6.9 Hz, 2H), 3.66-3.79 (m, 2H), 3.04-3.15 (m, 4H), 2.87 (s, 3H), 2.57-2.72 (m, 6H), 2.36-2.47 (m, 1H), 1.78-1.91 (m, 2H), 1.45-1.62 (m, 2H), 1.25 (t, J=7.0 Hz, 3H). MS (M−H, ES−) 806.

Workup

  1. concentrationThe reaction mixture was concentrated onto silica gel
  2. custompurified by flash chromatography
  3. customRecrystallization from DCM and diethyl ether

Sources & evidence

ORD record
ord-c6a3dbdb3111473dae524013542676b1
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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