p-Toluenesulfonic acid → HCID 59452720, compound

HRID 419534Notes

Reaction equation

HRID 419534 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].C1(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[CH2:47][CH2:48][N:49]([CH2:52][CH2:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH2:50][CH2:51]4)=[CH:39][C:40]=3[O:44][CH3:45])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH3:35]

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 59452720HCID 59452720, compoundYield 40%

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, 0.41 mmol), 5-methyl-2-(methyloxy)-4-{1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}aniline (120 mg, 0.37 mmol), and p-toluenesulfonic acid (186 mg, 0.98 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 (115 mg, 0.147 mmol, 40%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.79 (s, 1H), 9.40 (d, J=6.97 Hz, 1H), 8.47 (s, 1H), 8.26 (d, J=5.13 Hz, 1H), 8.11 (d, J=2.57 Hz, 1H), 7.78 (dd, J=8.43, 2.20 Hz, 1H), 7.71 (d, J=8.80 Hz, 1H), 7.56 (s, 1H), 7.42-7.49 (m, 1H), 7.34-7.42 (m, 1H), 7.28 (d, J=8.80 Hz, 1H), 7.18 (t, J=8.07 Hz, 2H), 6.97 (t, J=6.97 Hz, 1H), 6.89 (s, 1H), 6.59 (d, J=5.13 Hz, 1H), 3.99 (s, 3H), 3.81 (s, 3H), 3.28-3.32 (m, 2H), 3.06 (s, 3H), 3.02 (d, J=11.36 Hz, 2H), 2.74 (t, J=6.97 Hz, 2H), 2.60-2.70 (m, 1H), 2.20 (s, 3H), 2.04-2.15 (m, 2H), 1.65-1.76 (m, 4H). MS (ESI): 782 [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-d96393a6400c482cb5361dd864e66c63
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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