p-Toluenesulfonic acid → HCID 25124475, compound

HRID 419535Notes

Reaction equation

HRID 419535 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][C:37]1[C:38]([CH:46]2[CH2:51][CH2:50][N:49]([CH2:52][CH2:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH2:48][CH2:47]2)=[CH:39][C:40]([O:44][CH3:45])=[C:41]([CH:43]=1)[NH2:42].[C:58]1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)C(F)(F)F.C[O-].[Na+]>C(Cl)Cl>[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:42][C:41]3[CH:43]=[C:37]([CH3:36])[C:38]([CH:46]4[CH2:51][CH2:50][N:49]([CH2:52][CH2:53][S:54]([CH3:57])(=[O:55])=[O:56])[CH2:48][CH2:47]4)=[CH:39][C:40]=3[O:44][CH3:45])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH2:35][CH3:58]

Participants

7

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 64092,2,2-TrifluoroethanolHCID 10942334Sodium MethoxideHCID 594525905-(3-(2-chloropyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)-N-(2,6-difluorophenyl)-2-methoxybenzamideHCID 66649828HCID 66649828, compound

Product 1

HCID 25124475HCID 25124475, compoundYield 47.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °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) (200 mg, 0.4 mmol), 5-methyl-2-(methyloxy)-4-{1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}aniline (Example 163, step D) (117 mg, 0.36 mmol), and p-toluenesulfonic acid (180 mg, 0.95 mmol) were weighed into a 20 mL microwave vial. 7 mL of trifluoroethanol was added and the mixture was heated in the microwave to 150° C. for 2 h. The mixture was transferred to a 50 mL round bottom and neutralized with 2.5 mL of 0.5 N sodium methoxide. The solvent was rotovaped down. The residue was taken up in 10 mL of DCM. 2 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 (135 mg, 0.17 mmol, 43%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.74 (s, 1H), 9.39 (d, J=6.60 Hz, 1H), 8.46 (s, 1H), 8.26 (d, J=5.13 Hz, 1H), 8.05 (d, J=1.83 Hz, 1H), 7.74 (dd, J=8.62, 2.02 Hz, 1H), 7.70 (d, J=9.17 Hz, 1H), 7.56 (s, 1H), 7.41-7.49 (m, 1H), 7.37 (d, J=8.07 Hz, 1H), 7.26 (d, J=8.80 Hz, 1H), 7.19 (t, J=8.07 Hz, 2H), 6.96 (t, J=6.97 Hz, 1H), 6.89 (s, 1H), 6.58 (t, J=5.50 Hz, 1H), 4.26 (q, J=7.09 Hz, 2H), 3.79-3.82 (m, 3H), 3.26-3.36 (m, 2H), 3.06 (s, 3H), 3.02 (d, J=13.20 Hz, 4H), 2.68-2.76 (m, 2H), 2.59-2.68 (m, 1H), 2.20 (s, 3H), 2.02-2.14 (m, 2H), 1.65-1.76 (m, 2H), 1.43 (t, J=6.97 Hz, 3H). MS (ESI): 796 [M+H]+.

Workup

  1. addition2 g of silica gel was added
  2. customthe pre-adsorbed solids were purified by flash chromatography

Sources & evidence

ORD record
ord-15d3353866e14496a51217ae6ba74087
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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