p-Toluenesulfonic acid → 5-[3-(2-{[4-(1,4'-bipiperidin-1'-yl)-2-(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide

HRID 419331Notes

Reaction equation

HRID 419331 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.[N:36]1([CH:42]2[CH2:47][CH2:46][N:45]([C:48]3[CH:54]=[CH:53][C:51]([NH2:52])=[C:50]([O:55][CH3:56])[CH:49]=3)[CH2:44][CH2:43]2)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>CC(O)C>[N:36]1([CH:42]2[CH2:47][CH2:46][N:45]([C:48]3[CH:54]=[CH:53][C:51]([NH:52][C:2]4[N:7]=[C:6]([C:8]5[N:12]6[CH:13]=[CH:14][CH:15]=[CH:16][C:11]6=[N:10][C:9]=5[C:17]5[CH:18]=[CH:19][C:20]([O:34][CH3:35])=[C:21]([CH:33]=5)[C:22]([NH:24][C:25]5[C:26]([F:32])=[CH:27][CH:28]=[CH:29][C:30]=5[F:31])=[O:23])[CH:5]=[CH:4][N:3]=4)=[C:50]([O:55][CH3:56])[CH:49]=3)[CH2:44][CH2:43]2)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 594525905-(3-(2-chloropyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)-N-(2,6-difluorophenyl)-2-methoxybenzamideHCID 597120872-Methoxy-4-[4-(1-piperidyl)-1-piperidyl]aniline

Product 1

HCID 594529445-[3-(2-{[4-(1,4'-bipiperidin-1'-yl)-2-(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamideYield 53%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (Intermediate Example 2) (0.14 g, 0.28 mmol), 4-(1,4′-bipiperidin-1′-yl)-2-(methyloxy)aniline (Example 22, step C) (0.074 g, 0.25 mmol) and para-toluenesulfonic acid (0.12 g, 0.68 mmol) in iPrOH (5 mL) was heated at 180° C. for 10 min. The reaction was poured into half saturated NaHCO3, extracted with DCM and EtOAc, dried (MgSO4) and concentrated. Purification by flash chromatography followed by trituration with diethyl ether provided the title compound (0.099 g, 0.13 mmol, 53%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.36 (s, 3H), 1.46 (s, 4H), 1.49-1.58 (m, 2H), 1.77 (d, J=10.4 Hz, 2H), 2.29 (s, 3H), 2.62 (t, J=12.0 Hz, 2H), 3.72 (d, J=11.9 Hz, 3H), 3.77 (s, 3H), 3.97 (s, 3H), 6.41-6.52 (m, 2H), 6.64 (s, 1H), 6.93 (t, J=7.3 Hz, 1H), 7.16 (t, J=8.1 Hz, 2H), 7.26 (d, J=8.6 Hz, 1H), 7.32-7.43 (m, 3H), 7.67 (d, J=8.6 Hz, 1H), 7.75 (d, J=8.4 Hz, 1H), 8.08 (s, 1H), 8.13-8.21 (m, 1H), 8.42 (s, 1H), 9.34 (br. s., 1H), 9.76 (s, 1H). MS (M+H, ES+) 745.

Workup

  1. extractionextracted with DCM and EtOAc
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customPurification by flash chromatography

Sources & evidence

ORD record
ord-7f16f2f0882f47d796d9fadefbd4ba6a
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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