Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (R)-N-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

HRID 1517883Notes

Reaction equation

HRID 1517883 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][C:17]=1[F:23].[OH:24][C@H:25]([CH3:43])[CH2:26][N:27]1[C:31]([CH3:32])=[C:30]([C:33](O)=[O:34])[C:29](=[O:36])[N:28]1[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:33]([C:30]2[C:29](=[O:36])[N:28]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[N:27]([CH2:26][C@H:25]([OH:24])[CH3:43])[C:31]=2[CH3:32])=[O:34])=[CH:18][C:17]=1[F:23]

Participants

5

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 114269974-((6,7-Dimethoxyquinolin-4-yl)oxy)-3-fluorobenzenamineHCID 59383930(R)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid

Product 1

HCID 59598358(R)-N-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 85.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorobenzenamine (5.0 g, 0.016 mol) and (R)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (6.2 g, 0.022 mol) in CH2Cl2 (100 mL) at 0° C. was added TEA (5.5 g, 0.054 mol), followed by HATU (10.3 g, 0.027 mol) in portions. The reaction mixture was stirred at 0° C. for 2 h, warmed up to rt and continued to stir overnight. The reaction mixture was washed with water (30 mL×3). The organic phase was dried over Na2SO4 and concentrated in vacuo. The residue was crystallized in a mixture of EtOAc/n-hexane (50 mL, v/v=5:1) to give the title compound as a pale yellow solid (7.8 g, 85.2%).

Workup

  1. temperaturewarmed up to rt
  2. stirringto stir overnight
  3. washThe reaction mixture was washed with water (30 mL×3)
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was crystallized in a mixture of EtOAc/n-hexane (50 mL, v/v=5:1)

Sources & evidence

ORD record
ord-0154be7ca2d5443abc214c3d45243e66
Source dataset
uspto-grants-2012_07
Patent number
US08232294B2

Reaction notes

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