Triethylamine → N-[5-(dimethylamino)-1-(4-fluorophenyl)pyrazol-4-yl]-2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanamide

HRID 1754379Notes

Reaction equation

HRID 1754379 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([N:13]([CH3:15])[CH3:14])=[C:11]([NH2:16])[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:17][C:18]1[N:19]([CH:27]([CH3:31])[C:28](O)=[O:29])[CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[N:22]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>C(Cl)Cl.C(=O)(O)[O-].[Na+]>[CH3:15][N:13]([CH3:14])[C:12]1[N:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[N:9]=[CH:10][C:11]=1[NH:16][C:28](=[O:29])[CH:27]([N:19]1[CH:20]=[C:21]([C:23]([F:24])([F:26])[F:25])[N:22]=[C:18]1[CH3:17])[CH3:31]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867116772-[2-Methyl-4-(trifluoromethyl)imidazol-1-yl]propanoic acidHCID 867243832-(4-fluorophenyl)-N3,N3-dimethyl-pyrazole-3,4-diamine

Product 1

HCID 86724382N-[5-(dimethylamino)-1-(4-fluorophenyl)pyrazol-4-yl]-2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanamideYield 25%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of crude 2-(4-fluorophenyl)-N3,N3-dimethyl-pyrazole-3,4-diamine (from step b, 0.042 g, 0.18 mmol), 2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanoic acid (0.060 g, 0.27 mmol), HATU (0.10 g, 0.27 mmol), and 100 μL of Et3N in 1 mL of CH2Cl2 was stirred at room temperature. After 30 minutes, the reaction mixture was diluted with 10 mL of aqueous saturated sodium bicarbonate and extracted with EtOAc. The organic layer was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) afforded the title compound as a colorless solid (0.019 g, 0.045 mmol, 25% for 3 steps). 1H NMR (400 MHz, CDCl3) δ 7.77 (s, 1H), 7.53-7.43 (m, 2H), 7.27 (s, 1H), 7.17-7.08 (m, 2H), 6.91 (s, 1H), 4.90 (q, J=7.2 Hz, 1H), 2.53 (s, 6H), 2.45 (s, 3H), 1.85 (d, J=7.2 Hz, 3H). MS: (ES) m/z calculated for C19H20F4N6O1 [M+H]+ 424.2, found 424.1.

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-26c9448fdcc140bfbf58531aa028473a
Source dataset
uspto-grants-2015_10
Patent number
US09169248B2

Reaction notes

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