1,2-Diaminocyclohexane, trans- → 1-[4-(3-tert-Butyl-2-oxoimidazolidin-1-yl)-2-fluorophenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1624824Notes

Reaction equation

HRID 1624824 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]([N:33]1[CH2:37][CH2:36][NH:35][C:34]1=[O:38])([CH3:32])([CH3:31])[CH3:30].N[C@@H]1CCCC[C@H]1N.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I>[C:29]([N:33]1[CH2:37][CH2:36][N:35]([C:6]2[CH:5]=[CH:4][C:3]([N:9]3[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]4[N:22]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[N:21]=[CH:20][CH:19]=4)=[N:10]3)=[C:2]([F:1])[CH:7]=2)[C:34]1=[O:38])([CH3:32])([CH3:31])[CH3:30]

Participants

7

Reactant 4

HCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 27952311-Tert-butylimidazolidin-2-oneHCID 594362141-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Product 1

HCID 580723731-[4-(3-tert-Butyl-2-oxoimidazolidin-1-yl)-2-fluorophenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 39.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 1-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (488 mg, 1.0 mmol), 1-tert-butylimidazolidin-2-one (171 mg, 1.2 mmol), CuI (19 mg, 0.1 mmol), trans-1,2-diaminocyclohexane (0.024 mL, 0.2 mmol), and K3PO4 (425 mg, 2.0 mmol) in toluene (5 mL) was stirred at 80° C. for 24 h under N2 atmosphere. After cooling to room temperature, the reaction mixture was purified by silica gel column chromatography eluting with hexane/AcOEt (1/1), AcOEt only and then AcOEt/MeOH (10/1) and recrystallized from AcOEt to give the title compound (198 mg, 39% yield) as a white solid: mp 238-239° C.; 1H NMR (300 MHz, DMSO-d6): δ ppm 1.36 (9H, s), 3.29 (3H, s), 3.44-3.59 (2H, m), 3.64-3.76 (2H, m), 6.92-7.03 (2H, m), 7.23-7.51 (6H, m), 7.70 (1H, dd, J=14.1, 2.4 Hz), 7.78 (1H, d, J=1.9 Hz), 8.43 (1H, d, J=1.9 Hz). LC-MS (ESI) m/z 503 [M+H]+. Anal. Calcd for C27H27FN6O3: C, 64.53; H, 5.42; N, 16.72. Found: C, 64.31; H, 5.38; N, 16.58.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction mixture was purified by silica gel column chromatography
  3. washeluting with hexane/AcOEt (1/1), AcOEt only
  4. customAcOEt/MeOH (10/1) and recrystallized from AcOEt

Sources & evidence

ORD record
ord-c1b29fa59c1e4d4ea717f4dcedff6f18
Source dataset
uspto-grants-2014_07
Patent number
US08778944B2

Reaction notes

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