Diisopropylethylamine → N-[4-(2-Amino-5-{4-[(2R)-1,4-dioxan-2-ylmethoxy]-3-methoxyphenyl}pyridin-3-yl)phenyl]-1-(2-fluoroethyl)-4-oxo-5-phenyl-1,4-dihydropyridine-3-carboxamide

HRID 1428108Notes

Reaction equation

HRID 1428108 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][CH:22]=[CH:21][CH:20]=2)[C:16](=[O:25])[C:15]([C:26]([OH:28])=O)=[CH:14]1.CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F.[NH2:56][C:57]1[CH:62]=[CH:61][C:60]([C:63]2[C:64]([NH2:85])=[N:65][CH:66]=[C:67]([C:69]3[CH:74]=[CH:73][C:72]([O:75][CH2:76][C@H:77]4[CH2:82][O:81][CH2:80][CH2:79][O:78]4)=[C:71]([O:83][CH3:84])[CH:70]=3)[CH:68]=2)=[CH:59][CH:58]=1>CN(C=O)C.O>[NH2:85][C:64]1[C:63]([C:60]2[CH:59]=[CH:58][C:57]([NH:56][C:26]([C:15]3[C:16](=[O:25])[C:17]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[CH:18][N:13]([CH2:12][CH2:11][F:10])[CH:14]=3)=[O:28])=[CH:62][CH:61]=2)=[CH:68][C:67]([C:69]2[CH:74]=[CH:73][C:72]([O:75][CH2:76][C@H:77]3[CH2:82][O:81][CH2:80][CH2:79][O:78]3)=[C:71]([O:83][CH3:84])[CH:70]=2)=[CH:66][N:65]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 867000573-(4-Aminophenyl)-5-{4-[(2R)-1,4-dioxan-2-ylmethoxy]-3-methoxyphenyl}pyridin-2-amineHCID 867000611-(2-Fluoroethyl)-4-oxo-5-phenyl-1,4-dihydropyridine-3-carboxylic acid

Product 1

HCID 71698920N-[4-(2-Amino-5-{4-[(2R)-1,4-dioxan-2-ylmethoxy]-3-methoxyphenyl}pyridin-3-yl)phenyl]-1-(2-fluoroethyl)-4-oxo-5-phenyl-1,4-dihydropyridine-3-carboxamideYield 77.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (60 μl) was added to a solution of the compound obtained in Step 2 of Example 19 (50 mg) and COMU (96 mg) in DMF (3.0 ml) at room temperature, and the mixture was stirred for one hour. The compound obtained in Step 1 of Example 42 (70 mg) was added at room temperature. The mixture was stirred for five hours, followed by the addition of water. The organic layer was extracted with ethyl acetate, and then washed with water and brine and dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography [chloroform:methanol=19:1->9:1 (v/v)] to give 87 mg of the title compound as a solid.

Workup

  1. stirringThe mixture was stirred for five hours
  2. extractionThe organic layer was extracted with ethyl acetate
  3. washwashed with water and 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=19:1->9:1 (v/v)]

Sources & evidence

ORD record
ord-e118f17a05fb4dc296389d42a1e53b43
Source dataset
uspto-grants-2015_01
Patent number
US08933103B2

Reaction notes

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