p-Toluenesulfonic acid → N-(2,6-difluorophenyl)-3-(3-{2-[(5-methyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamide

HRID 419663Notes

Reaction equation

HRID 419663 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][C:35]1[C:36]([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:37][C:38]([O:42][CH3:43])=[C:39]([CH:41]=1)[NH2:40].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:40][C:39]3[CH:41]=[C:35]([CH3:34])[C:36]([N:44]4[CH2:49][CH2:48][CH:47]([N:50]5[CH2:51][CH2:52][N:53]([S:56]([CH3:59])(=[O:58])=[O:57])[CH2:54][CH2:55]5)[CH2:46][CH2:45]4)=[CH:37][C:38]=3[O:42][CH3:43])[N:7]=2)[CH:18]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 594526035-Methyl-2-(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 59452950N-(2,6-difluorophenyl)-3-(3-{2-[(5-methyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamideYield 35%

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) (0.050 g, 0.11 mmol), 5-methyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}aniline (Example 236, Step B) (0.041 g, 0.11 mmol) and para-toluenesulfonic acid (0.049 g, 0.26 mmol) in i-PrOH (5 mL) was heated in a microwave at 175° C. for 20 min. The reaction mixture was concentrated onto silica gel and purified by flash chromatography to afford the title compound (0.031 g, 35%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.24 (s, 1H), 9.42 (br. s., 1H), 8.48 (s, 1H), 8.34 (s, 1H), 8.25 (d, J=5.1 Hz, 1H), 8.06 (d, J=8.1 Hz, 1H), 7.83 (d, J=7.8 Hz, 1H), 7.75 (d, J=8.9 Hz, 1H), 7.62 (t, J=7.7 Hz, 1H), 7.34-7.55 (m, 3H), 7.17-7.29 (m, 2H), 6.95-7.06 (m, 1H), 6.77 (s, 1H), 6.51 (d, J=5.2 Hz, 1H), 3.80 (s, 3H), 3.05-3.17 (m, 6H), 2.88 (s, 3H), 2.59-2.73 (m, 6H), 2.38-2.46 (m, 1H), 2.16 (s, 3H), 1.81-1.90 (m, 2H), 1.53-1.68 (m, 2H). MS (M−H, ES−) 806.

Workup

  1. concentrationThe reaction mixture was concentrated onto silica gel
  2. custompurified by flash chromatography

Sources & evidence

ORD record
ord-3da8af26b49b49ada11c5eb7efadd388
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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