Water → HCID 59436271, compound

HRID 1407176Notes

Reaction equation

HRID 1407176 reaction equation
[F:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[N:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]2[N:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:21]=[CH:20][CH:19]=2)=[N:10]1.[C:29]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])(=[O:32])[NH:30][NH2:31].C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C.[Cu]I.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1>[F:1][C:2]1[CH:7]=[C:6]([N:30]([C:29]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[NH2:31])[CH:5]=[CH:4][C:3]=1[N:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]2[N:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:21]=[CH:20][CH:19]=2)=[N:10]1

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 70091tert-Butyl carbazateHCID 594362141-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Product 1

HCID 59436271HCID 59436271, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 13181,10-PhenanthrolineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 1-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (2.44 g, 5.0 mmol), tert-butyl carbazate (0.727 g, 5.5 mmol), CuI (0.0095 g, 0.05 mmol), 1,10-phenanthroline (0.072 g, 0.4 mmol), and Cs2CO3 (2.28 g, 7.0 mmol) in DMF (25 mL) was stirred for 5 h at 100° C. under Ar atmosphere. After cooling to room temperature, the reaction mixture was poured into water and extracted with AcOEt three times. The combined extracts were washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography eluting with AcOEt and crystallized from hexane/AcOEt to give the title compound (2.04 g, 83% yield) as a pale yellow solid: mp 163-165° C.; 1H NMR (300 MHz, CDCl3): δ ppm 1.58 (9H, s), 3.90 (3H, s), 4.36 (2H, s), 6.31 (1H, t, J=9.0 Hz), 7.28-7.45 (7H, m), 7.55 (1H, dd, J=2.3, 14.3 Hz), 7.78 (2H, d, J=1.9 Hz). Anal. Calcd for C25H25FN6O4: C, 60.97; H, 5.12; N, 17.06. Found: C, 61.20; H, 5.13; N, 16.81.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with AcOEt three times
  3. washThe combined extracts were washed with water and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography
  7. washeluting with AcOEt
  8. customcrystallized from hexane/AcOEt

Sources & evidence

ORD record
ord-2271744221344cc9a33943c55e1ea22f
Source dataset
uspto-grants-2014_12
Patent number
US08916566B2

Reaction notes

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