Sodium Hydroxide → (Rac)-3-[1-(6-fluoro-1-methyl-1h-indazol-5-yl)-ethyl]-6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazine

HRID 69279ノート

反応式

HRID 69279 の反応式
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][C:22]=3[F:23])[N:19]([CH3:24])[N:18]=[CH:17]4)(O)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.ClC1C=CC2N(C(C(C3C=[C:39]4[C:43](=CC=3F)[N:42]([CH3:47])[N:41]=[CH:40]4)C)=CN=2)N=1.[I-].O[PH2]=O.[OH-].[Na+]>C(O)(=O)C>[F:23][C:22]1[CH:21]=[C:20]2[C:16]([CH:17]=[N:18][N:19]2[CH3:24])=[CH:15][C:14]=1[CH:11]([C:8]1[N:6]2[N:7]=[C:2]([C:39]3[CH:40]=[N:41][N:42]([CH3:47])[CH:43]=3)[CH:3]=[CH:4][C:5]2=[N:10][CH:9]=1)[CH3:12]

参加物

6

反応物 4

HCID 14798Sodium HydroxideHCID 30165Iodide IonHCID 4124402Phosphinic AcidHCID 131731818HCID 131731818、化合物

生成物 1

HCID 57917432(Rac)-3-[1-(6-fluoro-1-methyl-1h-indazol-5-yl)-ethyl]-6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazine

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

実験手順

(rac)-6-Chloro-3-[1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (rac)-1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethanol (Stage 278.2, 2 g, 5.78 mmol) was dissolved in acetic acid (80 mL) and introduced in 4 microwave reactors. Iodide (1.84 g×4, 29 mmol), followed by H3PO2 50% (2.36 mL×4, 87 mmol) were then added into each reactor. Then they were submitted to microwave irradiations 5 min at 150° C. After combination, it was basified by a 2.5 M NaOH solution and extracted twice with EtOAc. The organics were joined and washed with brine, dried over Na2SO4 and the solvent was removed. The residue was purified by flash chromatography (CombiFlash® Companion System®, with 120 g RediSep® silica gel column, DCM/MeOH=100:0->94:6 in 30 min). The collected fractions containing product were evaporated and the residue was dried under vacuum to afford the title compound (tR 1.15 min (conditions 2), MH+=330).

後処理

  1. additionintroduced in 4 microwave reactors
  2. additionwere then added into each reactor
  3. customirradiations 5 min
  4. customat 150° C
  5. extractionextracted twice with EtOAc
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. customthe solvent was removed
  9. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with 120 g RediSep® silica gel column, DCM/MeOH=100:0->94:6 in 30 min)
  10. additionThe collected fractions containing product
  11. customwere evaporated
  12. customthe residue was dried under vacuum

出典と根拠

ORDレコード
ord-45cf5d9fdce545ca852ff8892b5314aa
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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