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

HRID 419482Notes

Reaction equation

HRID 419482 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]([CH2:43][CH2:44][CH2:45][N:46]2[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]2)[CH:40]=[CH:39][C:37]=1[NH2:38].C1(C)C=CC(S(O)(=O)=O)=CC=1.C[O-].[Na+]>C(Cl)Cl.CC(O)C>[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]([CH2:43][CH2:44][CH2:45][N:46]4[CH2:47][CH2:48][CH2:49][CH2:50][CH2:51]4)=[CH:42][C:36]=3[O:35][CH3:34])[N:7]=2)[CH:18]=1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 10942334Sodium MethoxideHCID 594528182-(Methyloxy)-4-[3-(1-piperidinyl)propyl]anilineHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

Product 1

HCID 59452597N-(2,6-difluorophenyl)-3-{3-[2-({2-(methyloxy)-4-[3-(1-piperidinyl)-propyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamideYield 37%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (110 mg, 0.24 mmol), 2-(methyloxy)-4-[3-(1-piperidinyl)propyl]aniline (57 mg, 0.21 mol), and p-toluenesulfonic acid (109 mg, 0.57 mmol) were weighed into a 20 mL vial. 7 mL of iPrOH was added and the mixture was heated to 120° C. for 40 h. The mixture was transferred to a 50 mL round bottom and neutralized with 2 mL of 0.5 N sodium methoxide. The solvent was rotovaped down. The residue was taken up in 10 mL of DCM. 1 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 (53 mg, 0.079 mmol, 37%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.23 (s, 1H), 9.40 (d, J=6.23 Hz, 1H), 8.51 (s, 1H), 8.33 (s, 1H), 8.25 (d, J=5.13 Hz, 1H), 8.04 (d, J=7.87 Hz, 1H), 7.81 (d, J=7.69 Hz, 1H), 7.73 (dd, J=8.88, 0.82 Hz, 1H), 7.56-7.64 (m, 2H), 7.45 (dd, J=8.52, 7.23 Hz, 1H), 7.35-7.42 (m, 1H), 7.19 (t, J=8.15 Hz, 2H), 6.99 (t, J=6.87 Hz, 1H), 6.93 (s, 1H), 6.74 (d, J=8.06 Hz, 1H), 6.52 (d, J=5.13 Hz, 1H), 3.81 (s, 3H), 2.56 (t, J=7.51 Hz, 2H), 2.20-2.31 (m, 6H), 1.68-1.77 (m, 2H), 1.41-1.50 (m, 4H), 1.30-1.40 (m, 2H). MS (ESI): 674 [M+H]+.

Workup

  1. addition1 g of silica gel was added
  2. customthe pre-adsorbed solids were purified by flash chromatography

Sources & evidence

ORD record
ord-860c9f57f56843ab987226c4f5e230fd
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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