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

HRID 419509Notes

Reaction equation

HRID 419509 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]=[CH:19][C:20]([O:34][CH3:35])=[C:21]([CH:33]=2)[C:22]([NH:24][C:25]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=2[F:32])=[O:23])[CH:5]=[CH:4][N:3]=1.[CH2:36]([O:38][C:39]1[CH:45]=[C:44]([N:46]2[CH2:51][CH2:50][N:49]([CH2:52][CH2:53][CH3:54])[CH2:48][CH2:47]2)[CH:43]=[CH:42][C:40]=1[NH2:41])[CH3:37].C1(C)C=CC(S(O)(=O)=O)=CC=1.C[O-].[Na+]>CC(O)C>[F:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[NH:24][C:22](=[O:23])[C:21]1[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:41][C:40]3[CH:42]=[CH:43][C:44]([N:46]4[CH2:51][CH2:50][N:49]([CH2:52][CH2:53][CH3:54])[CH2:48][CH2:47]4)=[CH:45][C:39]=3[O:38][CH2:36][CH3:37])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH3:35]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 10942334Sodium MethoxideHCID 594525905-(3-(2-chloropyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)-N-(2,6-difluorophenyl)-2-methoxybenzamideHCID 594526092-(Ethyloxy)-4-(4-propyl-1-piperazinyl)aniline

Product 1

HCID 59452787N-(2,6-difluorophenyl)-5-[3-(2-{[2-(ethyloxy)-4-(4-propyl-1-piperazinyl)phenyl]-amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-2-(methyloxy)benzamideYield 40%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
130 °C

Procedure

5-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (Intermediate Example 2) (100 mg, 0.2 mmol), 2-(ethyloxy)-4-(4-propyl-1-piperazinyl)aniline (48 mg, 0.18 mmol), and p-toluenesulfonic acid (93 mg, 0.49 mmol) were weighed into a 20 mL vial. 7 mL of iPrOH was added and the mixture was heated to 130° C. for 48 h. The mixture was transferred to a 50 mL round bottom and neutralized with 3 mL of 0.5 N sodium methoxide 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 (52 mg, 0.072 mmol, 40%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.78 (s, 1H), 9.32 (s, 1H), 8.35 (s, 1H), 8.21 (d, J=5.31 Hz, 1H), 8.09 (d, J=2.01 Hz, 1H), 7.76 (dd, J=8.61, 2.01 Hz, 1H), 7.68 (d, J=8.97 Hz, 1H), 7.35-7.45 (m, 3H), 7.26 (d, J=8.79 Hz, 1H), 7.17 (t, J=8.06 Hz, 2H), 6.92 (t, J=6.87 Hz, 1H), 6.64 (d, J=2.20 Hz, 1H), 6.53 (d, J=5.31 Hz, 1H), 6.46 (dd, J=8.79, 2.38 Hz, 1H), 4.04 (q, J=6.96 Hz, 2H), 3.97 (s, 3H), 3.07-3.13 (m, 4H), 2.43-2.51 (m, 4H), 2.26 (t, J=7.23 Hz, 2H), 1.40-1.50 (m, J=7.36, 7.36, 7.36, 7.36, 7.36 Hz, 2H), 1.22 (t, J=6.96 Hz, 3H), 0.85 (t, J=7.42 Hz, 3H). MS (ESI): 719 [M+H]+.

Workup

  1. additionwas added
  2. customthe pre-adsorbed solids were purified by flash chromatography

Sources & evidence

ORD record
ord-acfd87b53f7642a3b4b1cfc7221919c4
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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