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

HRID 1160001Notes

Reaction equation

HRID 1160001 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:34])[C:25]4[C:30]([F:31])=[CH:29][CH:28]=[C:27]([CH3:32])[C:26]=4[F:33])[CH:20]=[CH:21][CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.[NH2:35][C:36]1[CH:37]=[C:38]([O:42][CH2:43][CH2:44][N:45]([CH3:47])[CH3:46])[CH:39]=[CH:40][CH:41]=1>CC(O)C.Cl.C(Cl)Cl>[CH3:46][N:45]([CH3:47])[CH2:44][CH2:43][O:42][C:38]1[CH:37]=[C:36]([NH:35][C:2]2[N:7]=[C:6]([C:8]3[C:9]([C:17]4[CH:18]=[C:19]([NH:23][C:24](=[O:34])[C:25]5[C:30]([F:31])=[CH:29][CH:28]=[C:27]([CH3:32])[C:26]=5[F:33])[CH:20]=[CH:21][CH:22]=4)=[N:10][N:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=34)[CH:5]=[CH:4][N:3]=2)[CH:41]=[CH:40][CH:39]=1

Participants

6

Reactant 2

HCID 167782053-[2-(Dimethylamino)ethoxy]anilineHCID 86618785N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluoro-3-methylbenzamide

Product 1

HCID 11621459N-[3-(3-{2-[(3-{[2-(Dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2,6-difluoro-3-methylbenzamideYield 86%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluoro-3-methylbenzamide (100 mg, 0.21 mmol) (prepared in a manner similar to that described in Example 186) and {2-[(3-aminophenyl)oxy]ethyl}dimethylamine (47 mg, 0.26 mmol) in 2-propanol (3 mL) was added 2 drops of concentrated HCl. The reaction was stirred at 80° C. overnight. After 16 h, the mixture was diluted with DCM, washed with saturated aqueous NaHCO3, dried over Na2SO4, filtered, and adsorbed onto silica. The crude product was purified by column chromatography to generate the title compound in 86% yield (112 mg, 0.18 mmol). 1H NMR (400 MHz, d6-DMSO) δ 10.90 (s, 1H), 9.55 (s, 1H), 8.86 (d, J=6.7 Hz, 1H), 8.51 (d, J=8.6 Hz, 1H), 8.28 (d, J=5.2 Hz, 1H), 8.01 (s, 1H), 7.83 (d, J=7.9 Hz, 1H), 7.45-7.52 (m, 4H), 7.36 (d, J=7.3 Hz, 1H), 7.27 (d, J=8.1 Hz, 1H), 7.12-7.16 (m, 3H), 6.53 (d, J=5.1 Hz, 1H), 3.97 (t, J=5.6 Hz, 2H), 2.58 (t, J=5.8 Hz, 2H), 2.26 (s, 3H), 2.17 (s, 6H). MS (ESI) m/z=620 [M+H]+.

Workup

  1. customprepared in a manner similar to
  2. waitAfter 16 h
  3. washwashed with saturated aqueous NaHCO3
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-486be738d45e4ab9881d04fbba4fbd38
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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