Hydrochloric Acid → 5-(3-{2-[(3-{[2-(Dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}imidazo-[1,2-a]pyridin-2-yl)-2-(methyloxy)benzonitrile

HRID 419311Notes

Reaction equation

HRID 419311 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:25][CH3:26])=[C:21]([CH:24]=2)[C:22]#[N:23])[CH:5]=[CH:4][N:3]=1.Cl.Cl.[CH3:29][N:30]([CH3:41])[CH2:31][CH2:32][O:33][C:34]1[CH:35]=[C:36]([CH:38]=[CH:39][CH:40]=1)[NH2:37].Cl.C([O-])(O)=O.[Na+]>C(O)C(F)(F)F>[CH3:29][N:30]([CH3:41])[CH2:31][CH2:32][O:33][C:34]1[CH:35]=[C:36]([NH:37][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]=[CH:19][C:20]([O:25][CH3:26])=[C:21]([CH:24]=3)[C:22]#[N:23])[CH:5]=[CH:4][N:3]=2)[CH:38]=[CH:39][CH:40]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 594527785-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-2-(methyloxy)-benzonitrileHCID 66649609[2-(3-Aminophenoxy)ethyl]dimethylamine dihydrochloride

Product 1

HCID 594528045-(3-{2-[(3-{[2-(Dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}imidazo-[1,2-a]pyridin-2-yl)-2-(methyloxy)benzonitrileYield 93%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
84 °C

Procedure

To 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-2-(methyloxy)benzonitrile (Intermediate Example 4) (2.02 g, 5.57 mmol) and 3-{[2-(dimethylamino)ethyl]-oxy}aniline dihydrochloride (1.67 g, 6.58 mmol) in trifluoroethanol (20 mL) was added HCl (0.700 mL, 4M in dioxane, 2.8 mmol). The reaction was stirred at 84° C. for 2 days. The reaction was poured into half saturated NaHCO3, extracted with DCM and EtOAc, dried (MgSO4), concentrated and triturated with diethyl ether to provide the title compound (2.63 g, 5.18 mmol, 93%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.17 (s, 6H), 2.57 (t, J=5.7 Hz, 2H), 3.96 (s, 5H), 6.55 (d, J=8.4 Hz, 1H), 6.63 (d, J=5.1 Hz, 1H), 7.07 (t, J=7.0 Hz, 1H), 7.16 (t, J=8.1 Hz, 1H), 7.26 (d, J=8.4 Hz, 1H), 7.33 (d, J=9.2 Hz, 1H), 7.45-7.53 (m, 2H), 7.74 (d, J=9.2 Hz, 1H), 7.92 (dd, J=9.0, 2.0 Hz, 1H), 7.99 (d, J=1.8 Hz, 1H), 8.39 (d, J=5.1 Hz, 1H), 9.49 (d, J=6.2 Hz, 1H), 9.77 (s, 1H).

Workup

  1. extractionextracted with DCM and EtOAc
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-7f341b1b3e0245d3ad78157f0c6a7405
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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