p-Toluenesulfonic acid → N-(2,6-difluorophenyl)-3-(3-(2-(2-methoxy-4-(4-morpholinopiperidin-1-yl)phenylamino)pyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)benzamide

HRID 419349Notes

Reaction equation

HRID 419349 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][O:35][C:36]1[CH:42]=[C:41]([N:43]2[CH2:48][CH2:47][CH:46]([N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)[CH2:45][CH2:44]2)[CH:40]=[CH:39][C:37]=1[NH2:38].C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)C.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:38][C:37]3[CH:39]=[CH:40][C:41]([N:43]4[CH2:48][CH2:47][CH:46]([N:49]5[CH2:54][CH2:53][O:52][CH2:51][CH2:50]5)[CH2:45][CH2:44]4)=[CH:42][C:36]=3[O:35][CH3:34])[N:7]=2)[CH:18]=1

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 574161442-(Methyloxy)-4-[4-(4-morpholinyl)-1-piperidinyl]anilineHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

Product 1

HCID 44571814N-(2,6-difluorophenyl)-3-(3-(2-(2-methoxy-4-(4-morpholinopiperidin-1-yl)phenylamino)pyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)benzamideYield 66.7%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (139 mg, 0.30 mmol), 2-(methyloxy)-4-[4-(4-morpholinyl)-1-piperidinyl]aniline (79 mg, 0.27 mmol) and p-toluenesulfonic acid (137 mg, 0.71 mmol) in iPrOH was heated in the microwave at 180° C. for 13.5 min. The mixture was dissolved in DCM and concentrated onto silica gel. The crude material was purified by flash column chromatography to give 129 mg (60%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 10.22 (s, 1H), 9.38 (br s, 1H), 8.44 (s, 1H), 8.31 (s, 1H), 8.18 (d, J=5.2 Hz, 1H), 8.03 (d, J=8.0 Hz, 1H), 7.80 (d, J=8.0 Hz, 1H), 7.71 (d, J=9.2 Hz, 1H), 7.59 (t, J=7.8 Hz, 1H), 7.46-7.35 (m, 2H), 7.19 (t, J=8.0 Hz, 1H), 6.96 (t, J=6.8 Hz, 1H), 6.65 (m, 1H), 6.48-6.43 (m, 2H), 3.77 (s, 3H), 3.71 (d, J=12.4 Hz, 2H), 3.56-3.54 (M, 4H), 2.67-2.62 (m, 2H), 2.49-2.46 (m under DMSO peak, 4H), 2.27-2.22 (m, 1H), 1.86-1.83 (m, 2H), 1.52-1.44 (m, 2H). MS (ESI) m/z=717 [M+H]+.

Workup

  1. concentrationconcentrated onto silica gel
  2. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-0be5ac1492a54334801f0f7010e20000
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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