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

HRID 2059858노트

반응식

HRID 2059858 반응식
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

참가 물질

6

반응물 3

HCID 6422Trifluoroacetic acidHCID 58579880tert-butyl 4-iodo-6-oxopyridazine-1(6H)-carboxylateHCID 67134184Tributyl((4-chlorophenoxy)methyl)stannane

생성물 1

HCID 585798765-((4-chlorophenoxy)methyl)pyridazin-3(2H)-one수율 34.1%

시약·촉매·용매 2

HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매HCID 1140Toluene용매

반응 조건

온도
110 °C

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-62c8386a97c94cf79afb385dcda9971b
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08278316B2

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