Diisopropylethylamine → 6-fluoro-1-(1-(6-(1-methyl-1H-pyrazol-4-yl)pyridazin-3-yl)piperidin-4-yl)-1H-indazole

HRID 512864ノート

反応式

HRID 512864 の反応式
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[CH:4][CH:3]=1.Cl[C:18]1[N:19]=[N:20][C:21]([C:24]2[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=2)=[CH:22][CH:23]=1.CCN(C(C)C)C(C)C>CS(C)=O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][N:14]([C:18]3[N:19]=[N:20][C:21]([C:24]4[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=4)=[CH:22][CH:23]=3)[CH2:13][CH2:12]2)=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 539239646-fluoro-1-(piperidin-4-yl)-1H-indazoleHCID 545956073-Chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazine

生成物 1

HCID 763110986-fluoro-1-(1-(6-(1-methyl-1H-pyrazol-4-yl)pyridazin-3-yl)piperidin-4-yl)-1H-indazole

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

実験手順

6-Fluoro-1-(piperidin-4-yl)-1H-indazole (260 mg, 1.19 mmol), 3-chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazine (230 mg, 1.19 mmol) and DIEA (269 uL) in DMSO (4 ml) under Ar were heated in a microwave reactor at 200° C. for 1 hour. After removal of most of the DMSO in vacuo, water (10 mL) was added and the aqueous layer extracted several times with CHCl3 (50 mL). The organic layer was washed with brine, dried (MgSO4), decolorized with NORITE, filtered and the solvent removed in vacuo. The resulting residue was purified via ISCO column chromatography (Amine “Redisep” 14 gram column eluded 0-100% EtOAc/hexane over 20 column volumes), then re-crystallized from DCM with heptanes to yield 6-fluoro-1-(1-(6-(1-methyl-1H-pyrazol-4-yl)pyridazin-3-yl)piperidin-4-yl)-1H-indazole.

後処理

  1. customAfter removal of most of the DMSO in vacuo, water (10 mL)
  2. additionwas added
  3. extractionthe aqueous layer extracted several times with CHCl3 (50 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customThe resulting residue was purified via ISCO column chromatography (Amine “Redisep” 14 gram column eluded 0-100% EtOAc/hexane over 20 column volumes)
  9. customre-crystallized from DCM with heptanes

出典と根拠

ORDレコード
ord-8875cd278f3a47ff88de0577b4d32e7d
出典データセット
uspto-grants-2015_08
特許番号
US09102669B2

反応ノート

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