3-[2-(Dimethylamino)ethoxy]aniline → N-[3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}-4-fluoropyrazolo[1,5-a]pyridin-2-yl)phenyl]-2,6-difluorobenzamide

HRID 1159969Notes

Reaction equation

HRID 1159969 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:18]3[CH:19]=[C:20]([NH:24][C:25](=[O:34])[C:26]4[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=4[F:33])[CH:21]=[CH:22][CH:23]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=23)[CH:5]=[CH:4][N:3]=1.[CH3:35][N:36]([CH3:47])[CH2:37][CH2:38][O:39][C:40]1[CH:41]=[C:42]([CH:44]=[CH:45][CH:46]=1)[NH2:43]>C(O)(C)C.Cl>[CH3:35][N:36]([CH3:47])[CH2:37][CH2:38][O:39][C:40]1[CH:41]=[C:42]([NH:43][C:2]2[N:7]=[C:6]([C:8]3[C:9]([C:18]4[CH:19]=[C:20]([NH:24][C:25](=[O:34])[C:26]5[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=5[F:33])[CH:21]=[CH:22][CH:23]=4)=[N:10][N:11]4[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=34)[CH:5]=[CH:4][N:3]=2)[CH:44]=[CH:45][CH:46]=1

Participants

5

Reactant 2

HCID 167782053-[2-(Dimethylamino)ethoxy]anilineHCID 59513844N-{3-[3-(2-chloro-4-pyrimidinyl)-4-fluoropyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide

Product 1

HCID 59513725N-[3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}-4-fluoropyrazolo[1,5-a]pyridin-2-yl)phenyl]-2,6-difluorobenzamideYield 70%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 3776IsopropanolSolvent

Procedure

To the solution of N-{3-[3-(2-chloro-4-pyrimidinyl)-4-fluoropyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide (0.10 g) in isopropanol (6 mL) was added 3-{[2-(dimethylamino)ethyl]oxy}aniline (0.06 g) and 3 drops of concentrated hydrochloric acid. The reaction was microwaved in a sealed tube at 180° C. for 10 min. The isopropanol was removed by rotovaporation and the residue was treated with sat. NaHCO3 (5 mL), extracted with EtOAc (2×5 mL), and dried (Na2SO4). Concentration and purification with column chromatography afforded the title compound as a white solid (0.09 g, 70% yield). 1H NMR (400 MHz, CDCl3) 8 ppm 2.22 (s, 6H), 2.63 (t, J=5.6 Hz, 2H), 391 (t, J=5.6 Hz, 2H), 6.48 (dd, J=8.0, 1.7 Hz, 1H), 6.77 (td, J=7.2, 4.9 Hz, 1H), 6.82-6.85 (m, 1H), 6.86 (s, 1H), 6.89-6.94 (m, 3H), 7.00-7.07 (m, 1H), 7.21-7.32 (m, 4H), 7.43 (s, 1H), 7.79 (d, J=7.9 Hz, 1H), 7.90 (s, 1H), 8.33 (d, J=6.8 Hz, 1H), 8.35-8.38 (m, 1H), 8.45 (s, 1H); ESIMS (M+H)+=624.

Workup

  1. customThe reaction was microwaved in a sealed tube at 180° C. for 10 min
  2. customThe isopropanol was removed by rotovaporation
  3. additionthe residue was treated with sat. NaHCO3 (5 mL)
  4. extractionextracted with EtOAc (2×5 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationConcentration and purification with column chromatography

Sources & evidence

ORD record
ord-3aa4e170ba974f19a7316eb890d6b275
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

Loading…