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

HRID 419464Notes

Reaction equation

HRID 419464 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]([CH2:43][CH2:44][N:45]2[CH2:50][CH2:49][N:48]([CH3:51])[CH2:47][CH2:46]2)[CH:40]=[CH:39][C:37]=1[NH2:38].C1(C)C=CC(S(O)(=O)=O)=CC=1.C[O-].[Na+]>C(Cl)Cl.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]([CH2:43][CH2:44][N:45]4[CH2:46][CH2:47][N:48]([CH3:51])[CH2:49][CH2:50]4)=[CH:42][C:36]=3[O:35][CH3:34])[N:7]=2)[CH:18]=1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 10942334Sodium MethoxideHCID 574161632-Methoxy-4-[2-(4-methylpiperazin-1-yl)ethyl]anilineHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

Product 1

HCID 59452880N-(2,6-difluorophenyl)-3-{3-[2-({2-(methyloxy)-4-[2-(4-methyl-1-piperazinyl)ethyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamideYield 42.9%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
180 °C

Procedure

3-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (108 mg, 0.23 mmol), 2-(methyloxy)-4-[2-(4-methyl-1-piperazinyl)ethyl]aniline (Example 131, step D) (52 mg, 0.21 mmol), and p-toluenesulfonic acid (107 mg, 0.56 mmol) were weighed into a 10 mL microwave vial. 5 mL of iPrOH was added and the mixture was heated in the microwave to 180° C. for 17 min. The mixture was transferred to a 50 mL round bottom and neutralized with 1 mL of 0.5 N sodium methoxide. The solvent was rotovaped down. The residue was taken up in 10 mL of DCM. 1 g of silica gel was added. The solvent was rotovaped down and the pre-adsorbed solids were purified by flash chromatography to give the title compound (61 mg, 0.09 mmol, 37%). 1H NMR (400 MHz, CDCl3) δ ppm 9.47 (d, J=6.97 Hz, 1H), 8.27-8.31 (m, 2H), 8.26 (d, J=5.50 Hz, 1H), 7.98-8.06 (m, 2H), 7.81 (d, J=8.07 Hz, 1H), 7.71 (s, 1H), 7.67 (d, J=8.80 Hz, 1H), 7.51 (t, J=7.70 Hz, 1H), 7.32-7.40 (m, 1H), 7.18-7.26 (m, 1H), 6.98 (t, J=8.25 Hz, 2H), 6.89 (t, J=6.78 Hz, 1H), 6.78-6.84 (m, 2H), 6.60 (d, J=5.50 Hz, 1H), 3.93 (s, 3H), 2.76-2.85 (m, 2H), 2.43-2.75 (m, 10H), 2.32 (s, 3H). MS (ESI): 675 [M+H]+.

Workup

  1. addition1 g of silica gel was added
  2. customthe pre-adsorbed solids were purified by flash chromatography

Sources & evidence

ORD record
ord-37219bbf747749b28fe2e635e2b9126e
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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