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 69279노트

반응식

HRID 69279 반응식
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]

참가 물질

6

반응물 4

HCID 14798Sodium HydroxideHCID 30165Iodide IonHCID 4124402Phosphinic AcidHCID 131731818HCID 131731818, 화합물

생성물 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

시약·촉매·용매 1

HCID 176Acetic Acid용매

실험 절차

(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).

후처리

  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

출처 및 근거

ORD 기록
ord-45cf5d9fdce545ca852ff8892b5314aa
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822468B2

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