Triethylamine → N-(3-fluoro-4-(7-Methoxyquinolin-4-yloxy)phenyl)-1,2-dimethyl-3-oxo-5-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

HRID 415893Notes

Reaction equation

HRID 415893 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][N:26]1[C:30]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[C:29]([C:37]([OH:39])=O)[C:28](=[O:40])[N:27]1[CH3:41].[F:42][C:43]1[CH:44]=[C:45]([NH2:62])[CH:46]=[CH:47][C:48]=1[O:49][C:50]1[C:59]2[C:54](=[CH:55][C:56]([O:60][CH3:61])=[CH:57][CH:58]=2)[N:53]=[CH:52][CH:51]=1.C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[F:42][C:43]1[CH:44]=[C:45]([NH:62][C:37]([C:29]2[C:28](=[O:40])[N:27]([CH3:41])[N:26]([CH3:25])[C:30]=2[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)=[O:39])[CH:46]=[CH:47][C:48]=1[O:49][C:50]1[C:59]2[C:54](=[CH:55][C:56]([O:60][CH3:61])=[CH:57][CH:58]=2)[N:53]=[CH:52][CH:51]=1

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 583683541,2-dimethyl-3-oxo-5-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acidHCID 595983543-Fluoro-4-(7-methoxyquinolin-4-yloxy)benzenamine

Product 1

HCID 11962979N-(3-fluoro-4-(7-Methoxyquinolin-4-yloxy)phenyl)-1,2-dimethyl-3-oxo-5-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 35.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of HATU (458 mg, 1206 μmol), 1,2-dimethyl-3-oxo-5-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (140 mg, 603 μmol), 3-fluoro-4-(7-methoxyquinolin-4-yloxy)benzenamine (258 mg, 908 μmol), and Triethylamine (254 μL, 1809 mmol) in DMF (2 mL) was stirred at 60° C. overnight. The mixture was diluted with EtOAc (10 mL). The mixture was transferred to a separatory funnel with EtOAc (20 mL) and was washed with NaOH (1N, 10 mL), H2O (2×10 mL), NaHCO3 (sat), NaCl (sat), and dried over Na2SO4. The residue after concentration was purified on silica gel and the product was triturated with EtOAc-hexane (1:2) to afford a pink solid (106 mg, 35%). Calc'd for C28H23FN4O4: 498; MS (ESI pos. ion) m/z: 499 (MH+). 1HNMR (CDCl3, 400 MHz): 11.04 (1H, s), 8.56 (1H, d, J 5.3), 7.88 (1H, d, J 14.7), 7.55-7.40 (5H, m), 7.47 (1H, s), 7.35 (1H, d), 7.22 (1H, d, J9.1), 7.13 (1H, t, J 8.8), 6.36 (1H, d, J 5.3), 3.96 (3H, s), 3.62 (3H, s), 3.41 (3H, s).

Workup

  1. washwas washed with NaOH (1N, 10 mL), H2O (2×10 mL), NaHCO3 (sat), NaCl (sat)
  2. dry with materialdried over Na2SO4
  3. concentrationThe residue after concentration
  4. customwas purified on silica gel
  5. customthe product was triturated with EtOAc-hexane (1:2)

Sources & evidence

ORD record
ord-6c4a49f186634d909dbc335aa32fa027
Source dataset
uspto-grants-2012_01
Patent number
US08088794B2

Reaction notes

Loading…