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

HRID 419487Notes

Reaction equation

HRID 419487 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.[CH3:36][O:37][C:38]1[CH:44]=[C:43]([CH2:45][CH2:46][CH2:47][N:48]2[CH2:53][CH2:52][N:51]([CH3:54])[CH2:50][CH2:49]2)[CH:42]=[CH:41][C:39]=1[NH2:40].C1(C)C=CC(S(O)(=O)=O)=CC=1.C[O-].[Na+]>C(Cl)Cl.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:40][C:39]3[CH:41]=[CH:42][C:43]([CH2:45][CH2:46][CH2:47][N:48]4[CH2:49][CH2:50][N:51]([CH3:54])[CH2:52][CH2:53]4)=[CH:44][C:38]=3[O:37][CH3:36])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH3:35]

Participants

7

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 594529642-(Methyloxy)-4-[3-(4-methyl-1-piperazinyl)propyl]aniline

Product 1

HCID 59452581N-(2,6-difluorophenyl)-2-(methyloxy)-5-{3-[2-({2-(methyloxy)-4-[3-(4-methyl-1-piperazinyl)propyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamideYield 35%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °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) (110 mg, 0.22 mmol), 22-(methyloxy)-4-[3-(4-methyl-1-piperazinyl) propyl]aniline (Example 141, step B) (53 mg, 0.20 mol), and p-toluenesulfonic acid (102 mg, 0.54 mmol) were weighed into a 20 mL vial. 7 mL of iPrOH was added and the mixture was heated to 120° C. for 40 h. The mixture was transferred to a 50 mL round bottom and neutralized with 2 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 (50 mg, 0.07 mmol, 35%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.77 (s, 1H), 9.36 (d, J=6.78 Hz, 1H), 8.49 (s, 1H), 8.25 (d, J=5.13 Hz, 1H), 8.10 (d, J=2.20 Hz, 1H), 7.76 (dd, J=8.61, 2.20 Hz, 1H), 7.67-7.73 (m, 1H), 7.63 (d, J=7.87 Hz, 1H), 7.40-7.45 (m, 1H), 7.33-7.40 (m, 1H), 7.27 (d, J=8.79 Hz, 1H), 7.13-7.21 (m, 2H), 6.94-6.98 (m, 1H), 6.93 (d, J=1.65 Hz, 1H), 6.74 (dd, J=8.06, 1.65 Hz, 1H), 6.58 (d, J=5.31 Hz, 1H), 3.97 (s, 3H), 3.80 (s, 3H), 2.56 (t, J=7.60 Hz, 2H), 2.32-2.42 (m, 2H), 2.20-2.32 (m, 8H), 2.09-2.13 (m, 3H), 1.67-1.76 (m, 2H). MS (ESI): 719 [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-7bc8d68143ba494c95fbab98e18cd3b7
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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