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

HRID 419486Notes

Reaction equation

HRID 419486 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][CH2:45][N:46]2[CH2:51][CH2:50][N:49]([CH3:52])[CH2:48][CH2:47]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][CH2:45][N:46]4[CH2:47][CH2:48][N:49]([CH3:52])[CH2:50][CH2:51]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 594529642-(Methyloxy)-4-[3-(4-methyl-1-piperazinyl)propyl]anilineHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

Product 1

HCID 59452674N-(2,6-difluorophenyl)-3-{3-[2-({2-(methyloxy)-4-[3-(4-methyl-1-piperazinyl)propyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamideYield 34%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

3-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (110 mg, 0.24 mmol), 2-(methyloxy)-4-[3-(4-methyl-1-piperazinyl)propyl]aniline (56 mg, 0.21 mol), and p-toluenesulfonic acid (109 mg, 0.57 mmol) were weighed into a 20 mL vial. 7 mL of iPrOH was added and the mixture was heated to 120° C. for 40 hours. 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, 0.073 mmol, 34%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.22 (s, 1H), 9.39 (d, J=6.59 Hz, 1H), 8.50 (s, 1H), 8.31-8.34 (m, 1H), 8.25 (d, J=5.31 Hz, 1H), 8.02-8.06 (m, 1H), 7.79-7.82 (m, 1H), 7.73 (d, J=8.97 Hz, 1H), 7.56-7.64 (m, 2H), 7.45 (ddd, J=8.88, 6.78, 1.19 Hz, 1H), 7.35-7.41 (m, 1H), 7.20 (td, J=8.06, 5.13 Hz, 2H), 6.98 (t, J=6.87 Hz, 1H), 6.93 (d, J=1.47 Hz, 1H), 6.74 (dd, J=8.15, 1.56 Hz, 1H), 6.52 (d, J=5.13 Hz, 1H), 3.80 (s, 3H), 2.56 (t, J=7.60 Hz, 2H), 2.32-2.42 (m, 2H), 2.21-2.32 (m, 8H), 2.11 (s, 3H), 1.67-1.76 (m, 2H). MS (ESI): 689 [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-f87575dafc4b4b20833cf66880adac1c
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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