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

HRID 419528Notes

Reaction equation

HRID 419528 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]([CH:45]2[CH2:50][CH2:49][N:48]([CH2:51][CH:52]([CH3:54])C)[CH2:47][CH2:46]2)[CH:42]=[CH:41][C:39]=1[NH2:40].[C:55]1(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]=[C:42]([CH3:55])[C:43]([CH:45]4[CH2:46][CH2:47][N:48]([CH2:51][CH2:52][CH3:54])[CH2:49][CH2:50]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 59452706{2-(Methyloxy)-4-[1-(2-methylpropyl)-4-piperidinyl]phenyl}amine

Product 1

HCID 59452784n-(2,6-Difluorophenyl)-5-[3-(2-{[5-methyl-2-(methyloxy)-4-(1-propyl-4-piperidinyl)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-2-(methyloxy)-benzamideYield 40%

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) (100 mg, 0.2 mmol), 2-(methyloxy)-4-[1-(2-methylpropyl)-4-piperidinyl]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 120° 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. 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 (52 mg, 0.072 mmol, 40%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.78 (s, 1H), 9.37 (d, J=6.59 Hz, 1H), 8.50 (s, 1H), 8.24 (d, J=5.13 Hz, 1H), 8.10 (d, J=2.01 Hz, 1H), 7.76 (dd, J=8.61, 2.20 Hz, 1H), 7.69 (d, J=8.97 Hz, 1H), 7.65 (d, J=8.06 Hz, 1H), 7.40-7.46 (m, 1H), 7.32-7.40 (m, 1H), 7.27 (d, J=8.79 Hz, 1H), 7.17 (t, J=8.06 Hz, 2H), 6.93-6.98 (m, 2H), 6.78 (dd, J=8.24, 1.47 Hz, 1H), 6.58 (d, J=5.31 Hz, 1H), 3.97 (s, 3H), 3.82 (s, 3H), 2.90 (d, J=10.07 Hz, 2H), 2.38-2.46 (m, 1H), 1.98-2.08 (m, 2H), 1.87-1.98 (m, 2H), 1.65-1.76 (m, 5H), 0.84 (d, J=6.41 Hz, 6H). MS (ESI): 718 [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-8524efeb0f5e4b49b39c45c386266bae
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

Loading…