Diisopropylethylamine → N-(4-((3-Chloro-2-((diphenylmethylene)amino)pyridin-4-yl)oxy)-3-fluorophenyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide

HRID 408049Notes

Reaction equation

HRID 408049 reaction equation
[NH2:1][C:2]1[CH:29]=[CH:28][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([N:13]=[C:14]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:8]=2[Cl:27])=[C:4]([F:30])[CH:3]=1.[F:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[C:39](=[O:47])[C:40]([C:44](O)=[O:45])=[CH:41][NH:42][CH:43]=2)=[CH:34][CH:33]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:27][C:8]1[C:9]([N:13]=[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:10][CH:11]=[CH:12][C:7]=1[O:6][C:5]1[CH:28]=[CH:29][C:2]([NH:1][C:44]([C:40]2[C:39](=[O:47])[C:38]([C:35]3[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=3)=[CH:43][NH:42][CH:41]=2)=[O:45])=[CH:3][C:4]=1[F:30]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581336014-(4-amino-2-fluorophenoxy)-3-chloro-N-(diphenylmethylene)pyridin-2-amineHCID 602042075-(4-Fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid

Product 1

HCID 86650689N-(4-((3-Chloro-2-((diphenylmethylene)amino)pyridin-4-yl)oxy)-3-fluorophenyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamideYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(4-amino-2-fluorophenoxy)-3-chloro-N-(diphenylmethylene) pyridin-2-amine (836 mg, 2.0 mmol) and 5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid (490 mg, 2.0 mmol) in DMF (10 mL) at room temperature were added HATU (913 mg, 2.4 mmol) and DIPEA (1.05 ml, 6.0 mmol). The reaction mixture was stirred at room temperature for 3 h prior to being quenched by the addition of cold water (50 mL). The solid that formed was collected by filtration, and washed with water and ether. The solid was dissolved in DCM and purified by flash column chromatography (SiO2, DCM to 10% MeOH in DCM) to give the desired product (987 mg, 78%) as a light yellow solid. MS (ESI) m/z 633 (M+H)+.

Workup

  1. customto being quenched by the addition of cold water (50 mL)
  2. customThe solid that formed
  3. filtrationwas collected by filtration
  4. washwashed with water and ether
  5. dissolutionThe solid was dissolved in DCM
  6. custompurified by flash column chromatography (SiO2, DCM to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-672025d5f537472289297debdbc6fc16
Source dataset
uspto-grants-2014_06
Patent number
US08754230B2

Reaction notes

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