1-Hydroxybenzotriazole → N-{4-[2-Amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]phenyl}-5-(4-fluorophenyl)-4-oxo-1-(2,2,2-trifluoroethyl)-1,4-dihydropyridine-3-carboxamide

HRID 1428112Notes

Reaction equation

HRID 1428112 reaction equation
C1C=CC2N(O)N=NC=2C=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.[F:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]2[C:52](=[O:65])[C:53]([C:62](O)=[O:63])=[CH:54][N:55]([CH2:57][C:58]([F:61])([F:60])[F:59])[CH:56]=2)=[CH:47][CH:46]=1.[NH2:66][C:67]1[CH:72]=[CH:71][C:70]([C:73]2[C:74]([NH2:85])=[N:75][CH:76]=[C:77]([C:79]3[CH:80]=[N:81][N:82]([CH3:84])[CH:83]=3)[CH:78]=2)=[CH:69][CH:68]=1>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[NH2:85][C:74]1[C:73]([C:70]2[CH:69]=[CH:68][C:67]([NH:66][C:62]([C:53]3[C:52](=[O:65])[C:51]([C:48]4[CH:49]=[CH:50][C:45]([F:44])=[CH:46][CH:47]=4)=[CH:56][N:55]([CH2:57][C:58]([F:61])([F:60])[F:59])[CH:54]=3)=[O:63])=[CH:72][CH:71]=2)=[CH:78][C:77]([C:79]2[CH:80]=[N:81][N:82]([CH3:84])[CH:83]=2)=[CH:76][N:75]=1

Participants

9

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867000505-(4-Fluorophenyl)-4-oxo-1-(2,2,2-trifluoroethyl)-1,4-dihydropyridine-3-carboxylic acidHCID 867000643-(4-Aminophenyl)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine

Product 1

HCID 86700065N-{4-[2-Amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]phenyl}-5-(4-fluorophenyl)-4-oxo-1-(2,2,2-trifluoroethyl)-1,4-dihydropyridine-3-carboxamideYield 30.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

HOBt (51 mg), HATU (215 mg), DMAP (23 mg) and DIPEA (131 μl) were added to a solution of the Compound obtained in Step 2 of Example 9 (131 mg) in DMF (2 ml) at room temperature. The reaction mixture was stirred at room temperature for 1.5 hours. The compound obtained in Step 1 of Example 47 (100 mg) was added to the reaction mixture at room temperature. The reaction mixture was stirred at 50° C. for 1.5 hours and returned to room temperature. Water was added to the reaction mixture, and the precipitated solid was collected by filtration. The resulting solid was purified by PLC [dichloromethane:methanol=15:1 (v/v)] to give 64 mg of the title compound as a solid.

Workup

  1. stirringThe reaction mixture was stirred at 50° C. for 1.5 hours
  2. customreturned to room temperature
  3. filtrationthe precipitated solid was collected by filtration
  4. customThe resulting solid was purified by PLC [dichloromethane:methanol=15:1 (v/v)]

Sources & evidence

ORD record
ord-5cff4277cd064f038b33257ed1383555
Source dataset
uspto-grants-2015_01
Patent number
US08933103B2

Reaction notes

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