Triethylamine → N-(4-(1-(4-methoxybenzyl)-3-(4-(2-methoxyethyl)piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

HRID 2241414Notes

Reaction equation

HRID 2241414 reaction equation
CCN=C=NCCCN(C)C.[F:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[C:24](=[O:25])[C:23]([C:26]([OH:28])=O)=[CH:22][CH:21]=[N:20]2)=[CH:15][CH:14]=1.[CH3:29][O:30][C:31]1[CH:65]=[CH:64][C:34]([CH2:35][N:36]2[C:40]3=[N:41][CH:42]=[CH:43][C:44]([O:45][C:46]4[CH:51]=[CH:50][C:49]([NH2:52])=[CH:48][C:47]=4[F:53])=[C:39]3[C:38]([N:54]3[CH2:59][CH2:58][N:57]([CH2:60][CH2:61][O:62][CH3:63])[CH2:56][CH2:55]3)=[N:37]2)=[CH:33][CH:32]=1.C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[CH3:29][O:30][C:31]1[CH:32]=[CH:33][C:34]([CH2:35][N:36]2[C:40]3=[N:41][CH:42]=[CH:43][C:44]([O:45][C:46]4[CH:51]=[CH:50][C:49]([NH:52][C:26]([C:23]5[C:24](=[O:25])[N:19]([C:16]6[CH:15]=[CH:14][C:13]([F:12])=[CH:18][CH:17]=6)[N:20]=[CH:21][CH:22]=5)=[O:28])=[CH:48][C:47]=4[F:53])=[C:39]3[C:38]([N:54]3[CH2:59][CH2:58][N:57]([CH2:60][CH2:61][O:62][CH3:63])[CH2:56][CH2:55]3)=[N:37]2)=[CH:64][CH:65]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 667671712-(4-Fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acidHCID 685138364-(1-(4-methoxybenzyl)-3-(4-(2-methoxyethyl)piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine

Product 1

HCID 68513921N-(4-(1-(4-methoxybenzyl)-3-(4-(2-methoxyethyl)piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamideYield 10%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

EDCI (27 mg, 0.14 mmol) was added to a stirred mixture of 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (11 mg, 0.047 mmol, prepared according to the procedure described for Example 19, Step C) and HOBt-hydrate (22 mg, 0.14 mmol) in DMF (0.3 mL) at ambient temperature, and the reaction mixture was stirred for 15 minutes at ambient temperature. 4-(1-(4-Methoxybenzyl)-3-(4-(2-methoxyethyl)piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (12 mg, 0.024 mmol) and triethylamine (0.020 ml, 0.14 mmol) were then added, and the resulting mixture was stirred for 18 hours at ambient temperature. The reaction mixture was diluted with EtOAc and washed with water. The aqueous phase was re-extracted with EtOAc. The combined organic phases were washed with water, dried (Na2SO4), filtered, and concentrated in vacuo. The crude material was purified by preparative TLC (0.5 mm) and eluted with 15% MeOH/DCM (Rf=0.74). The product was obtained as a waxy solid (2 mg, 10%).

Workup

  1. customprepared
  2. customat ambient temperature
  3. stirringthe resulting mixture was stirred for 18 hours at ambient temperature
  4. washwashed with water
  5. extractionThe aqueous phase was re-extracted with EtOAc
  6. washThe combined organic phases were washed with water
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified by preparative TLC (0.5 mm)
  11. washeluted with 15% MeOH/DCM (Rf=0.74)

Sources & evidence

ORD record
ord-d3bbcb1bc4b34aa192ee2fb316c6ad56
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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