Diisopropylethylamine → N-(4-{3-amino-6-[2-(4-morpholinyl)-4-pyridinyl]-2-pyrazinyl}phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

HRID 1853096Notes

Reaction equation

HRID 1853096 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[C:5]([C:8]([OH:10])=O)[C:4](=[O:11])[N:3]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:51][C:52]1[CH:57]=[CH:56][C:55]([C:58]2[C:59]([NH2:76])=[N:60][CH:61]=[C:62]([C:64]3[CH:69]=[CH:68][N:67]=[C:66]([N:70]4[CH2:75][CH2:74][O:73][CH2:72][CH2:71]4)[CH:65]=3)[N:63]=2)=[CH:54][CH:53]=1>C(Cl)Cl.CN(C=O)C.O>[NH2:76][C:59]1[C:58]([C:55]2[CH:56]=[CH:57][C:52]([NH:51][C:8]([C:5]3[C:4](=[O:11])[N:3]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)[N:2]([CH3:1])[C:6]=3[CH3:7])=[O:10])=[CH:53][CH:54]=2)=[N:63][C:62]([C:64]2[CH:69]=[CH:68][N:67]=[C:66]([N:70]3[CH2:75][CH2:74][O:73][CH2:72][CH2:71]3)[CH:65]=2)=[CH:61][N:60]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 246564Antipyric acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682888223-(4-Aminophenyl)-5-[2-(4-morpholinyl)-4-pyridinyl]-2-pyrazinamine

Product 1

HCID 68289162N-(4-{3-amino-6-[2-(4-morpholinyl)-4-pyridinyl]-2-pyrazinyl}phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 82.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To the compound prepared in Example 1 (0.100 g) in 5 mL of DCM, 1.0 mL of DMF and N,N-diisopropylethylamine (DIEA) (0.072 g) was added the HATU (0.164 g) and stirred for 30 minutes. To the activated ester was added the compound prepared in Example 13 (0.15 g) and stirred for 1 hour. The reaction mixture was diluted with water, extracted with additional DCM, and the organic layer was washed with water, brine and dried over anhydrous Na2SO4. The DCM layer was filtered and concentrated, and the crude was chromatographed on silica gel using 10:1 DCM:MeOH to give the title compound (0.2 g) having the following physical data.

Workup

  1. stirringstirred for 1 hour
  2. extractionextracted with additional DCM
  3. washthe organic layer was washed with water, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationThe DCM layer was filtered
  6. concentrationconcentrated
  7. customthe crude was chromatographed on silica gel using 10:1 DCM

Sources & evidence

ORD record
ord-335b95ccc5c94fd798393012b9a8b798
Source dataset
uspto-grants-2015_02
Patent number
US08962623B2

Reaction notes

Loading…