Triethylamine → N-{3-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-2-fluoro-5-methylbenzamide

HRID 589911

反応式

HRID 589911 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(N(CC)CC)C.[C:19]([C:21]1[CH:22]=[C:23]([NH:27][C:28](=[O:37])[C:29]2[CH:34]=[C:33]([CH3:35])[CH:32]=[CH:31][C:30]=2[F:36])[CH:24]=[CH:25][CH:26]=1)#[CH:20]>CN(C=O)C.C(OCC)(=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:20]#[C:19][C:21]3[CH:22]=[C:23]([NH:27][C:28](=[O:37])[C:29]4[CH:34]=[C:33]([CH3:35])[CH:32]=[CH:31][C:30]=4[F:36])[CH:24]=[CH:25][CH:26]=3)=[N:7][N:6]2[CH:8]=1

参加物

8

反応物 3

HCID 8471TriethylamineHCID 574410246-Iodoimidazo[1,2-B]pyridazin-2-amineHCID 62510676N-(3-ethynylphenyl)-2-fluoro-5-methylbenzamide

生成物 1

HCID 118638430N-{3-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-2-fluoro-5-methylbenzamide

試薬・触媒・溶媒 4

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HCID 8857Ethyl Acetate溶媒

実験手順

To the nitrogen bubbled solution of 6-iodo-imidazo[1,2-b]pyridazin-2-ylamine (52 mg, 0.2 mmol, 1 eq) in anhydrous DMF (2 mL) was added triethylamine (0.11 mL, 4 eq), bis(triphenylphosphine)palladium(II) dichloride (14 mg, 0.1 eq), copper(I) iodide (7.6 mg, 0.2 eq), and N-(3-ethynylphenyl)-2-fluoro-5-methylbenzamide (76 mg, 1.5 eq). after the mixture was stirred at room temperature for 30 minutes, it was diluted with ethyl acetate, washed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, brine, and lastly dried with anhydrous sodium sulfate. The upper solution was decanted, concentrated, and the solid residue was subject to a gradient column chromatography [EtOAc-Hex 1:2 to 3:1 (with 1% v/v MeOH added)]. The product fractions were collected, concentrated, the residue was further triturated with ethyl acetate to give N-{3-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-2-fluoro-5-methylbenzamide as a yellow solid in amount of 23 mg.

後処理

  1. washwashed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, brine
  2. dry with materiallastly dried with anhydrous sodium sulfate
  3. customThe upper solution was decanted
  4. concentrationconcentrated
  5. additionadded)]
  6. customThe product fractions were collected
  7. concentrationconcentrated
  8. customthe residue was further triturated with ethyl acetate

出典と根拠

ORDレコード
ord-8499f186f1824029b761d9b7de5f6208
出典データセット
uspto-grants-2016_01
特許番号
US09233968B1

関連ノート

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