p-Toluenesulfonic acid → HCID 59452893, compound

HRID 419491Notes

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

Participants

Conditions

Temperature: 130 °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) (300 mg, 0.61 mmol), a different batch of 2-(ethyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}aniline (180 mg, 0.55 mmol), and p-toluenesulfonic acid (278 mg, 1.46 mmol) were weighed into a 40 mL vial. 25 mL of iPrOH was added and the mixture was heated to 130° C. for 48 h. The mixture was transferred to a 50 mL round bottom and neutralized with 5 mL of 0.5 N sodium methoxide. The solvent was rotovaped down. The residue was taken up in 30 mL of DCM. 3 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 (190 mg, 0.242 mmol, 44%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.77 (s, 1H), 9.31 (s, 1H), 8.35 (s, 1H), 8.21 (d, J=5.31 Hz, 1H), 8.09 (d, J=2.20 Hz, 1H), 7.76 (dd, J=8.61, 2.20 Hz, 1H), 7.68 (d, J=8.97 Hz, 1H), 7.35-7.46 (m, 3H), 7.26 (d, J=8.79 Hz, 1H), 7.17 (t, J=8.06 Hz, 2H), 6.92 (t, J=6.68 Hz, 1H), 6.66 (d, J=2.38 Hz, 1H), 6.53 (d, J=5.13 Hz, 1H), 6.47 (dd, J=8.61, 2.38 Hz, 1H), 4.05 (q, J=7.08 Hz, 2H), 3.97 (s, 3H), 3.31-3.34 (m, 2H), 3.08-3.15 (m, 4H), 3.02 (s, 3H), 2.74 (t, J=6.78 Hz, 2H), 2.51-2.60 (m, 4H), 1.22 (t, J=6.96 Hz, 3H). MS (ESI): 783 [M+H]+.

Workup

addition3 g of silica gel was added
customthe pre-adsorbed solids were purified by flash chromatography

Sources & evidence

ORD record: ord-3bfe8bd391624dfeac1dc7c6dcf5eefb
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093239B2

Reaction notes

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