Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 11963219, compound

HRID 2359667Notes

Reaction equation

HRID 2359667 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].[CH3:24][N:25]1[C:29]([C:30]2[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=2)=[C:28]([C:36](O)=[O:37])[C:27](=[O:39])[N:26]1[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.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:36]([C:28]2[C:27](=[O:39])[N:26]([C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=3)[N:25]([CH3:24])[C:29]=2[C:30]2[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=2)=[O:37])=[CH:18][C:17]=1[F:23]

Participants

6

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 59598434HCID 59598434, compound

Product 1

HCID 11963219HCID 11963219, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorobenzenamine (628.9 mg, 2.001 mmol) and 1-methyl-3-oxo-2-phenyl-5-(pyridin-4-yl)-2,3-dihydro-1H-pyrazole-4-carboxylic acid (520 mg, 1.76 mmol) (1.679 g of a ˜30% by weight solution of acid in DMF) was dissolved in DCM (20 ml) and HATU (1.042 g, 2.740 mmol) was added. The reaction was stirred under nitrogen at room temperature overnight, and then filtered. The filtered solid was washed with dichloromethane, and the filtrate was concentrated and purified on silica gel (DCM→50:1→25:1→10:1 DCM/MeOH). The fractions with product were collected, concentrated, and purified on silica gel (30:1→20:1→10:1 DCM/MeOH). Fractions with product collected, concentrated, and purified again on silica gel (25:1→20:1 DCM/MeOH). Fractions with pure product collected and concentrated to give desired N-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-1-methyl-3-oxo-2-phenyl-5-(pyridin-4-yl)-2,3-dihydro-1H-pyrazole-4-carboxamide (225.9 mg, 0.382 mmol, 22% yield). MS (ESI pos. ion) m/z: 592 (MH+). Calc'd exact mass for C33H26FN5O5: 591. 1H NMR (400 MHz, CDCl3): 10.96 (s, 1H), 8.88 (d, J=4.0 Hz, 2H), 8.48 (d, J=6.0 Hz, 1H), 7.83 (d, J=12 Hz, 1H), 7.65-7.47 (m, 8H), 7.41 (s, 1H), 7.30 (d, J=10.0 Hz, 1H), 7.16 (t, J=8.0 Hz, 1H), 6.40 (d, J=5.2 Hz, 1H), 4.05 (s, 6H), 3.20 (s, 3H).

Workup

  1. filtrationfiltered
  2. washThe filtered solid was washed with dichloromethane
  3. concentrationthe filtrate was concentrated
  4. custompurified on silica gel (DCM→50:1→25:1→10:1 DCM/MeOH)
  5. customThe fractions with product were collected
  6. concentrationconcentrated
  7. custompurified on silica gel (30:1→20:1→10:1 DCM/MeOH)
  8. customFractions with product collected
  9. concentrationconcentrated
  10. custompurified again on silica gel (25:1→20:1 DCM/MeOH)
  11. customFractions with pure product collected
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-8613ef4f9e874741906da2564134bdc4
Source dataset
uspto-grants-2014_04
Patent number
US08685983B2

Reaction notes

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