Triethylamine → 1-{4-[(2-Aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-3-(3-methylphenyl)urea

HRID 589896

反応式

HRID 589896 の反応式
I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH2:11])[N:10]=2)[N:7]=1.[C:12]([C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[CH:25]=2)=[O:22])=[CH:16][CH:15]=1)#[CH:13].C(N(CC)CC)C>CN(C=O)C.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.[Cu]I>[NH2:11][C:9]1[N:10]=[C:5]2[CH:4]=[CH:3][C:2]([C:13]#[C:12][C:14]3[CH:15]=[CH:16][C:17]([NH:20][C:21]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[CH:25]=4)=[O:22])=[CH:18][CH:19]=3)=[N:7][N:6]2[CH:8]=1

参加物

7

反応物 3

HCID 8471TriethylamineHCID 574410246-Iodoimidazo[1,2-B]pyridazin-2-amineHCID 1186384341-(4-Ethynylphenyl)-3-(3-methylphenyl)urea

生成物 1

HCID 1186384141-{4-[(2-Aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-3-(3-methylphenyl)urea

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒

実験手順

To a nitrogen bubbled solution of 6-iodo-imidazo[1,2-b]pyridazin-2-ylamine (260 mg, 1 mmol, 1 eq) and 1-(4-ethynylphenyl)-3-(3-methylphenyl)urea (375 mg, 1.5 eq) in DMF (5 mL) was added triethylamine (0.56 mL, 4 eq), bis(triphenylphosphine)palladium(II) dichloride (70.2 mg, 0.1 eq), and copper(I) iodide (38.1 mg, 0.2 eq). The reaction mixture was stirred at room temperature for 10 minutes and then partitioned between saturated aq NaHCO3 and i-PrOH—CHCl3 (1:4). The aqueous layer was extracted once more with i-PrOH—CHCl3 (1:4). The two organic layers were combined, washed with brine, and dried with anhydrous Na2SO4. The upper clear liquid was decanted, concentrated with silica gel, and the solid mixture was chromatographed (eluted from DCM to MeOH-DCM 1:15). The product fractions were collected and concentrated. The solid residue was triturated with EtOAc-Hex (1:1) and gave 1-{4-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-3-(3-methylphenyl)urea as a brown solid upon filtration in amount of 133 mg.

後処理

  1. custompartitioned between saturated aq NaHCO3 and i-PrOH—CHCl3 (1:4)
  2. extractionThe aqueous layer was extracted once more with i-PrOH—CHCl3 (1:4)
  3. washwashed with brine
  4. dry with materialdried with anhydrous Na2SO4
  5. customThe upper clear liquid was decanted
  6. concentrationconcentrated with silica gel
  7. customthe solid mixture was chromatographed
  8. wash(eluted from DCM to MeOH-DCM 1:15)
  9. customThe product fractions were collected
  10. concentrationconcentrated
  11. customThe solid residue was triturated with EtOAc-Hex (1:1)

出典と根拠

ORDレコード
ord-23b537517f624047ab6905b106169cff
出典データセット
uspto-grants-2016_01
特許番号
US09233968B1

関連ノート

読み込み中…