Trifluoroacetic acid → 5-((4-chlorophenoxy)methyl)pyridazin-3(2H)-one

HRID 2059858Notes

Reaction equation

C([Sn](CCCC)(CCCC)[CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1)CCC.I[C:24]1[CH:25]=[N:26][N:27](C(OC(C)(C)C)=O)[C:28](=[O:30])[CH:29]=1.C(O)(C(F)(F)F)=O>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:14][C:11]1[CH:10]=[CH:9][C:8]([O:7][CH2:6][C:24]2[CH:25]=[N:26][NH:27][C:28](=[O:30])[CH:29]=2)=[CH:13][CH:12]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of tributyl((4-chlorophenoxy)methyl)stannane (29.5 mg, 0.068 mmol), tert-butyl 4-iodo-6-oxopyridazine-1(6H)-carboxylate (20 mg, 0.062 mmol) and bis(triphenylphosphine)palladium(II)chloride (2.18 mg, 3.10 μmol) in toluene (1.0 mL) under nitrogen in a sealed tube was stirred at 110° C. for 2 hours. After removal of the precipitate, the filtrate was concentrated and dissolved in CH2Cl2 (3.0 mL). After addition of TFA (1.0 mL, 12.98 mmol), the solution was stirred at RT for 15 min before being concentrated. The crude product was purified by prep-HPLC (C18 column/Water:MeOH:TFA 90:10:0.1 to 10:90:0.1 gradient) to give 5-((4-chlorophenoxy)methyl)pyridazin-3(2H)-one 8B (5.0 mg, 33% yield). 1H NMR (400 MHz, THF-D8) δ ppm 5.99 (1H, d, J=1.76 Hz), 5.55 (2H, d, J=8.78 Hz), 5.27 (2H, d, J=9.03 Hz), 5.08 (1H, d, J=1.51 Hz), 3.24 (2H, s).

Workup

customAfter removal of the precipitate
concentrationthe filtrate was concentrated
dissolutiondissolved in CH2Cl2 (3.0 mL)
stirringthe solution was stirred at RT for 15 min
concentrationbefore being concentrated
customThe crude product was purified by prep-HPLC (C18 column/Water:MeOH:TFA 90:10:0.1 to 10:90:0.1 gradient)

Sources & evidence

ORD record: ord-62c8386a97c94cf79afb385dcda9971b
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278316B2

Reaction notes

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