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

HRID 2059858ノート

反応式

HRID 2059858 の反応式
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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6102075Dichlorobis(triphenylphosphine)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
110 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-62c8386a97c94cf79afb385dcda9971b
出典データセット
uspto-grants-2012_10
特許番号
US08278316B2

反応ノート

読み込み中…