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

HRID 1754378Notes

Reaction equation

HRID 1754378 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([O:13][CH:14]([CH3:16])[CH3:15])=[C:11]([NH2:17])[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:18][C:19]1[N:20]([CH:28]([CH3:32])[C:29](O)=[O:30])[CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[N:23]=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+]>[CH:14]([O:13][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:17][C:29](=[O:30])[CH:28]([N:20]1[CH:21]=[C:22]([C:24]([F:25])([F:27])[F:26])[N:23]=[C:19]1[CH3:18])[CH3:32])([CH3:15])[CH3:16]

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 867243811-(4-Fluorophenyl)-5-isopropoxy-pyrazol-4-amine

Product 1

HCID 76902777N-[5-isopropoxy-1-(4-fluorophenyl)pyrazol-4-yl]-2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanamideYield 52.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of crude 1-(4-fluorophenyl)-5-isopropoxy-pyrazol-4-amine (prepared in step b, 0.032 g, 0.13 mmol), 2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanoic acid (0.031 g, 0.13 mmol), HATU (0.057 g, 0.13 mmol), and 100 μL of Et3N in 1 mL of CH2Cl2 was stirred at room temperature. After 30 min, 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) provided the title compound as a colorless solid (0.030 g, 0.068 mmol, 52% for 3 steps). 1H NMR (400 MHz, CD3OD) δ 7.81 (s, 1H), 7.70 (s, 1H), 7.68-7.57 (m, 2H), 7.30-7.19 (m, 2H), 5.16 (q, J=6.5 Hz, 1H), 4.26 (he, J=6.1 Hz, 1H), 2.47 (s, 3H), 1.80 (d, J=6.5 Hz, 3H), 1.14 (d, J=6.1, 6 H). MS: (ES) m/z calculated for C20H21F4N5O2 [M+H]+ 439.2, found 439.4.

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-1aa01553b7d84937965ac81e54c79e19
Source dataset
uspto-grants-2015_10
Patent number
US09169248B2

Reaction notes

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