Isopropanol → Methyl 3-{3-[2-({5-fluoro-2-(methyloxy)-4-[2-(1-piperidinyl)ethyl]phenyl]amino)-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl}benzoate

HRID 419453Notes

Reaction equation

HRID 419453 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:24]=[CH:25][CH:26]=2)[C:20]([O:22][CH3:23])=[O:21])[CH:5]=[CH:4][N:3]=1.[F:27][C:28]1[C:29]([CH2:37][CH2:38][N:39]2[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]2)=[CH:30][C:31]([O:35][CH3:36])=[C:32]([CH:34]=1)[NH2:33].C1(C)C=CC(S(O)(=O)=O)=CC=1.CC(O)C>C(Cl)Cl>[F:27][C:28]1[C:29]([CH2:37][CH2:38][N:39]2[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]2)=[CH:30][C:31]([O:35][CH3:36])=[C:32]([NH:33][C:2]2[N:7]=[C:6]([C:8]3[N:12]4[CH:13]=[CH:14][CH:15]=[CH:16][C:11]4=[N:10][C:9]=3[C:17]3[CH:18]=[C:19]([CH:24]=[CH:25][CH:26]=3)[C:20]([O:22][CH3:23])=[O:21])[CH:5]=[CH:4][N:3]=2)[CH:34]=1

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 6101p-Toluenesulfonic acidHCID 59452862Methyl 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzoateHCID 594529305-Fluoro-2-(methyloxy)-4-[2-(1-piperidinyl)ethyl]aniline

Product 1

HCID 59452635Methyl 3-{3-[2-({5-fluoro-2-(methyloxy)-4-[2-(1-piperidinyl)ethyl]phenyl]amino)-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl}benzoateYield 51.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
180 °C

Procedure

Methyl 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzoate (Intermediate Example 3) (300 mg, 0.82 mmol), 5-fluoro-2-(methyloxy)-4-[2-(1-piperidinyl)ethyl]aniline (Example 127, step D) (187 mg, 0.74 mmol), and p-toluenesulfonic acid (375 mg, 1.97 mmol) were weighed into a 10 mL microwave vial. 7 mL of iPrOH was added and the mixture was heated in the microwave to 180° C. for 17 min. The mixture was transferred to a 50 mL round bottom and diluted with 10 mL of DCM. 2 g of silica gel was added. The solvent was rotovaped down and the residue purified by flash chromatography to give the title compound of step A (220 mg, 0.38 mmol, 46%). 1H NMR (400 MHz, CDCl3) δ ppm 9.51 (d, J=6.97 Hz, 1H), 8.37-8.39 (m, 1H), 8.23-8.30 (m, 2H), 8.08-8.11 (m, 1H), 7.84-7.87 (m, 1H), 7.79 (s, 1H), 7.74 (d, J=8.80 Hz, 1H), 7.50 (t, J=7.70 Hz, 1H), 7.35-7.41 (m, 1H), 6.95 (t, J=6.97 Hz, 1H), 6.76 (d, J=6.97 Hz, 1H), 6.60 (d, J=5.50 Hz, 1H), 3.91 (s, 3H), 3.90 (s, 3H), 2.79-2.86 (m, 2H), 2.54-2.60 (m, 2H), 2.46-2.54 (m, 4H), 1.60-1.66 (m, J=5.68, 5.68, 5.68, 5.68 Hz, 4H), 1.43-1.50 (m, J=5.13 Hz, 2H).

Workup

  1. addition2 g of silica gel was added
  2. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-fd393a6893f842daa64c27dba9c468da
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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