Trifluoroacetic acid → 5,7-Difluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline

HRID 69260노트

반응식

HRID 69260 반응식
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[CH:21][C:22]4[N:23]([C:25]([CH2:28][C:29]5[C:30]([F:40])=[C:31]6[C:36](=[CH:37][C:38]=5[F:39])[N:35]=[CH:34][CH:33]=[CH:32]6)=[CH:26][N:27]=4)[N:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:40][C:30]1[C:29]([CH2:28][C:25]2[N:23]3[N:24]=[C:19]([C:17]4[CH:16]=[N:15][N:14]([CH:11]5[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]5)[CH:18]=4)[CH:20]=[CH:21][C:22]3=[N:27][CH:26]=2)=[C:38]([F:39])[CH:37]=[C:36]2[C:31]=1[CH:32]=[CH:33][CH:34]=[N:35]2

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 579173924-{4-[3-(5,7-Difluoro-quinolin-6-yl methyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 579174245,7-Difluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

4-{4-[3-(5,7-Difluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (Example 244, 219 mg, 0.401 mmol) was dissolved in DCM (3 mL) with TFA (0.619 mL, 8.03 mmol). The RM was stirred at rt for 1 h 15 min and it was quenched with ice water. It was extracted with EtOAc twice. The combined organic layers was washed with brine and dried over Na2SO4. It was filtered and the solvent was removed. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The fractions were joined and the acetonitrile was removed. The aqueous solution was basified with 5% NaHCO3 solution and was extracted with EtOAc twice. Combined organic layers was washed with brine and dried over Na2SO4. It was filtered to afford after evaporation of the solvent the title compound as a white solid (tR 0.8 min (conditions 2), MH+=446).

후처리

  1. customit was quenched with ice water
  2. extractionIt was extracted with EtOAc twice
  3. washThe combined organic layers was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationIt was filtered
  6. customthe solvent was removed
  7. customThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
  8. customthe acetonitrile was removed
  9. extractionwas extracted with EtOAc twice
  10. washCombined organic layers was washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationIt was filtered
  13. customto afford
  14. customafter evaporation of the solvent the title compound as a white solid (tR 0.8 min (conditions 2), MH+=446)

출처 및 근거

ORD 기록
ord-b007b7d312614a3b8b9f8d7259c08b88
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822468B2

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