Water → 1-{6-[6-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-imidazo[1,2-a]pyridin-3-yl}-ethanol

HRID 69300ノート

反応式

HRID 69300 の反応式
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]3[N:11]([C:13]([CH2:16][C:17]4[CH:18]=[CH:19][C:20]5[N:21]([C:23]([C:26](=[O:28])[CH3:27])=[CH:24][N:25]=5)[CH:22]=4)=[CH:14][N:15]=3)[N:12]=2)[CH:4]=[N:3]1.O.[BH4-].[Na+].O1CCOCC1>CO>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]3[N:11]([C:13]([CH2:16][C:17]4[CH:18]=[CH:19][C:20]5[N:21]([C:23]([CH:26]([OH:28])[CH3:27])=[CH:24][N:25]=5)[CH:22]=4)=[CH:14][N:15]=3)[N:12]=2)[CH:4]=[N:3]1

参加物

6

反応物 4

HCID 962WaterHCID 312751,4-DioxaneHCID 4311764Sodium borohydride2 回HCID 57917427HCID 57917427、化合物

生成物 1

HCID 579172831-{6-[6-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-imidazo[1,2-a]pyridin-3-yl}-ethanol

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

1-{6-[6-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-imidazo[1,2-a]pyridin-3-yl}-ethanone (Example 301, 50 mg, 0.135 mmol) was dissolved in MeOH (3 mL) and water (1 mL) then NaBH4 (3.1 mg, 0.081 mmol) was added. The RM was stirred at rt for 2 h. More equivalents of NaBH4 (3 times 5.1 mg, 0.135 mmol) were added to RM over 18 h. Then dioxane was added and it was stirred at 60° C. for 2 h. It was quenched with EtOAc and solvents were removed. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The fractions were joined and lyophilized. The residue was dissolved in MeOH and it was passed through an SPE cartridge of HCO3− to remove the TFA salt. The filtrate was evaporated to give the free salt compound of the title compound as a white solid (tR 0.6 min (conditions 2), MH+=374).

後処理

  1. stirringit was stirred at 60° C. for 2 h
  2. customIt was quenched with EtOAc and solvents
  3. customwere removed
  4. customThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
  5. dissolutionThe residue was dissolved in MeOH
  6. customto remove the TFA salt
  7. customThe filtrate was evaporated

出典と根拠

ORDレコード
ord-7100ae2075f541b3b8535c56e3af226d
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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