Triethylamine → 1-[3-(Trifluoromethyl)phenyl]-3-[(trimethylsilyl)ethynyl]pyridazin-4(1H)-one

HRID 1895132Notes

Reaction equation

HRID 1895132 reaction equation
Br[C:2]1[C:7](=[O:8])[CH:6]=[CH:5][N:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[N:3]=1.[CH3:19][Si:20]([C:23]#[CH:24])([CH3:22])[CH3:21].CCN(CC)CC>[Cl-].[Na+].O.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:16][C:15]([F:18])([F:17])[C:11]1[CH:10]=[C:9]([N:4]2[CH:5]=[CH:6][C:7](=[O:8])[C:2]([C:24]#[C:23][Si:20]([CH3:22])([CH3:21])[CH3:19])=[N:3]2)[CH:14]=[CH:13][CH:12]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 66111Trimethylsilylacetylene3×HCID 58072447HCID 58072447, compound

Product 1

HCID 580725071-[3-(Trifluoromethyl)phenyl]-3-[(trimethylsilyl)ethynyl]pyridazin-4(1H)-oneYield 28%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 3-bromo-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (500 mg, 1.57 mmol), (trimethylsilyl)acetylene (0.222 mL, 1.57 mmol), Et3N (0.329 mL, 2.36 mmol), CuI (4.5 mg, 0.0236 mmol), Pd(PPh3)2Cl2 (55.1 mg, 0.0785 mmol) and PPh3 (10.3 mg, 0.0393 mmol) in TI-IF (7.5 mL) was heated to 40° C. for 8 h under Ar. To the suspension was added (trimethylsilyl)acetylene (0.111 mL, 0.785 mmol). The suspension was heated to 40° C. for 14 h under Ar. To the suspension was added (trimethylsilyl)acetylene (0.0888 mL, 0.628 mmol). The suspension was heated to 40° C. for 96 h under Ar. The mixture was diluted with brine, extracted with EtOAc, dried over MgSO4, filtered, concentrated in vacuo and purified by column chromatography on silica gel (hexane/EtOAc=50/50 to 0/100) to yield the title compound (148 mg, 28% yield) as a brown solid: 1H NMR (DMSO-d6, 300 MHz): δ ppm 0.26 (9H, s), 6.64 (1H, d, J=7.9 Hz), 7.75-7.92 (2H, m), 8.00-8.15 (2H, m), 8.90 (1H, d, J=8.3 Hz).

Workup

  1. temperatureThe suspension was heated to 40° C. for 14 h under Ar
  2. temperatureThe suspension was heated to 40° C. for 96 h under Ar
  3. extractionextracted with EtOAc
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography on silica gel (hexane/EtOAc=50/50 to 0/100)

Sources & evidence

ORD record
ord-8b8ec130ad454bd7bae50622b3a96fe9
Source dataset
uspto-grants-2013_08
Patent number
US08513251B2

Reaction notes

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