Hydrochloric Acid → 2-{4-[3-(6-Fluoro-1-methyl-1H-indazol-5-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-ethanol

HRID 69283ノート

反応式

HRID 69283 の反応式
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH3:11])=[CH:4][C:3]=1[CH2:12][C:13]1[N:17]2[N:18]=[C:19]([C:22]3[CH:23]=[N:24][N:25]([CH2:27][CH2:28][O:29]C4CCCCO4)[CH:26]=3)[CH:20]=[CH:21][C:16]2=[N:15][CH:14]=1.Cl>C(Cl)Cl.O1CCOCC1>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH3:11])=[CH:4][C:3]=1[CH2:12][C:13]1[N:17]2[N:18]=[C:19]([C:22]3[CH:23]=[N:24][N:25]([CH2:27][CH2:28][OH:29])[CH:26]=3)[CH:20]=[CH:21][C:16]2=[N:15][CH:14]=1

参加物

5

反応物 2

HCID 313Hydrochloric AcidHCID 690748973-(6-Fluoro-1-methyl-1H-indazol-5-ylmethyl)-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazine

生成物 1

HCID 579172712-{4-[3-(6-Fluoro-1-methyl-1H-indazol-5-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-ethanol

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

実験手順

3-(6-Fluoro-1-methyl-1H-indazol-5-yl methyl)-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazine (Stage 281.1, 269 mg, 566 μmol) was dissolved in DCM (5 mL). HCl in dioxane (4 N, 283 μl) was added and the RM was stirred 1 h at rt. The solvent was totally evaporated and the residue was taken up with EtOAc and washed with saturated NaHCO3 and brine. The organic layer was dried over Na2SO4 and solvent evaporated under vacuo. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The acetonitrile was removed and the aqueous solution was basified with 5% NaHCO3. It was extracted 3 times with EtOAc and then the organics were joined and washed with brine. It was dried over Na2SO4 and the solvent was removed. The residue was triturated with pentane and the precipitate was filtered off to give the title compound a white solid (tR 0.93 min (conditions 2), MH+=392, 1H-NMR in DMSO-d6: 8.42 (s, 1H); 8.1 (s, 1H); 8.02 (d, 1H); 7.97 (s, 1H); 7.75 (d, 1H); 7.52 (t, 3H); 4.95 (m, 1H); 4.40 (s, 2H); 4.21 (t, 2H); 3.96 (s, 3H); 3.77 (m, 2H)).

後処理

  1. customThe solvent was totally evaporated
  2. washwashed with saturated NaHCO3 and brine
  3. dry with materialThe organic layer was dried over Na2SO4 and solvent
  4. customevaporated under vacuo
  5. customThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
  6. customThe acetonitrile was removed
  7. extractionIt was extracted 3 times with EtOAc
  8. washwashed with brine
  9. dry with materialIt was dried over Na2SO4
  10. customthe solvent was removed
  11. customThe residue was triturated with pentane
  12. filtrationthe precipitate was filtered off

出典と根拠

ORDレコード
ord-923216118eea4a13b2172815ab21bc5d
出典データセット
uspto-grants-2014_09
特許番号
US08822468B2

反応ノート

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