p-Toluenesulfonic acid → HCID 59452656, compound

HRID 419463Notes

Reaction equation

HRID 419463 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][N:47]2[CH2:52][CH2:51][N:50]([CH3:53])[CH2:49][CH2:48]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][N:47]4[CH2:48][CH2:49][N:50]([CH3:53])[CH2:51][CH2:52]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 574161632-Methoxy-4-[2-(4-methylpiperazin-1-yl)ethyl]anilineHCID 594525905-(3-(2-chloropyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)-N-(2,6-difluorophenyl)-2-methoxybenzamide

Product 1

HCID 59452656HCID 59452656, compoundYield 76.7%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
180 °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-[2-(4-methyl-1-piperazinyl)ethyl]aniline (46 mg, 0.18 mmol), and p-toluenesulfonic acid (93 mg, 0.49 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 (97 mg, 0.138 mmol, 68%). 1H NMR (400 MHz, CDCl3) δ ppm 9.52 (d, J=6.97 Hz, 1H), 9.29 (s, 1H), 8.63 (d, J=2.20 Hz, 1H), 8.30 (d, J=8.80 Hz, 1H), 8.23 (d, J=5.13 Hz, 1H), 7.87 (dd, J=8.43, 2.57 Hz, 1H), 7.66-7.75 (m, 2H), 7.30-7.38 (m, 1H), 7.15-7.23 (m, 1H), 7.13 (d, J=8.80 Hz, 1H), 6.94-7.01 (m, 2H), 6.84-6.90 (m, 1H), 6.78-6.82 (m, 2H), 6.64 (d, J=5.13 Hz, 1H), 4.11 (s, 3H), 3.92 (s, 3H), 2.75-2.86 (m, 2H), 2.43-2.74 (m, 10H), 2.32 (s, 3H). MS (ESI): 705 [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-ec6ac994299c4e5c846a10bfe36fafc5
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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