Diisopropylethylamine → N-[4-(2-Amino-5-bromopyridin-3-yl)phenyl]-1-(2-fluoroethyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide

HRID 1428107Notes

Reaction equation

HRID 1428107 reaction equation
CCN(C(C)C)C(C)C.[F:10][CH2:11][CH2:12][N:13]1[CH:18]=[C:17]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[C:16](=[O:26])[C:15]([C:27]([OH:29])=O)=[CH:14]1.CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F.[NH2:57][C:58]1[CH:63]=[CH:62][C:61]([C:64]2[C:65]([NH2:71])=[N:66][CH:67]=[C:68]([Br:70])[CH:69]=2)=[CH:60][CH:59]=1>CN(C=O)C.O>[NH2:71][C:65]1[C:64]([C:61]2[CH:60]=[CH:59][C:58]([NH:57][C:27]([C:15]3[C:16](=[O:26])[C:17]([C:19]4[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=4)=[CH:18][N:13]([CH2:12][CH2:11][F:10])[CH:14]=3)=[O:29])=[CH:63][CH:62]=2)=[CH:69][C:68]([Br:70])=[CH:67][N:66]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 682889763-(4-Aminophenyl)-5-bromopyridin-2-amineHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 867000601-(2-Fluoroethyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid

Product 1

HCID 86700059N-[4-(2-Amino-5-bromopyridin-3-yl)phenyl]-1-(2-fluoroethyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamideYield 81.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (114 μl) was added to a solution of the compound obtained in Step 2 of Example 8 (91 mg) and COMU (181 mg) in DMF (2.0 ml) at room temperature, and the mixture was stirred for 20 minutes. The compound obtained in Step 1 of Example 1 (95 mg) was added at room temperature. The mixture was stirred for six hours, followed by the addition of water. After extraction with ethyl acetate, the organic layer was washed with brine and then dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography [chloroform:methanol=300:1->30:1 (v/v)] to give 139 mg of the title compound as a solid.

Workup

  1. stirringThe mixture was stirred for six hours
  2. extractionAfter extraction with ethyl acetate
  3. washthe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe residue was purified by silica gel column chromatography [chloroform:methanol=300:1->30:1 (v/v)]

Sources & evidence

ORD record
ord-ab457a7f35314049ad14cc0f5086d06e
Source dataset
uspto-grants-2015_01
Patent number
US08933103B2

Reaction notes

Loading…