p-Toluenesulfonic acid → HCID 59452975, compound

HRID 419536Notes

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][C:35]1[C:36]([CH:44]2[CH2:49][CH2:48][N:47]([CH2:50][CH2:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH2:46][CH2:45]2)=[CH:37][C:38]([O:42][CH3:43])=[C:39]([CH:41]=1)[NH2:40].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)C(F)(F)F.C[O-].[Na+]>C(Cl)Cl>[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:40][C:39]3[CH:41]=[C:35]([CH3:34])[C:36]([CH:44]4[CH2:45][CH2:46][N:47]([CH2:50][CH2:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH2:48][CH2:49]4)=[CH:37][C:38]=3[O:42][CH3:43])[N:7]=2)[CH:18]=1

Participants

Conditions

Temperature: 150 °C

Procedure

3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (200 mg, 0.43 mmol), 5-methyl-2-(methyloxy)-4-{1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}aniline (Example 163, step D) (127 mg, 0.39 mmol), and p-toluenesulfonic acid (197 mg, 1 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 1 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 10.22 (s, 1H), 9.41 (d, J=6.04 Hz, 1H), 8.47 (s, 1H), 8.32 (s, 1H), 8.24 (d, J=5.31 Hz, 1H), 8.04 (d, J=7.69 Hz, 1H), 7.80 (d, J=7.87 Hz, 1H), 7.72 (d, J=8.97 Hz, 1H), 7.59 (t, J=7.69 Hz, 1H), 7.53 (s, 1H), 7.43-7.49 (m, 1H), 7.39 (t, J=8.06 Hz, 1H), 7.19 (t, J=8.06 Hz, 2H), 6.98 (t, J=6.87 Hz, 1H), 6.88 (s, 1H), 6.51 (d, J=5.13 Hz, 1H), 3.80 (s, 3H), 3.27-3.30 (m, 2H), 3.05 (s, 3H), 2.98-3.03 (m, 2H), 2.73 (t, J=6.87 Hz, 2H), 2.59-2.68 (m, 1H), 2.18 (s, 3H), 2.03-2.14 (m, 2H), 1.64-1.74 (m, 4H). MS (ESI): 752 [M+H]+.

Workup

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

Sources & evidence

ORD record: ord-98dc3f8dbde8446986a839d4e51cd0ae
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093239B2

Reaction notes

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