Ethyl Acetate → (Rac)-2-(4-{3-[1-(5,7-difluoro-quinolin-6-yl)-ethyl]-imidazo[1,2-b]pyridazin-6-yl}-pyrazol-1-yl)ethanol

HRID 69223노트

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HRID 69223 반응식
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[C:14]([F:24])=[C:15]4[C:20](=[CH:21][C:22]=3[F:23])[N:19]=[CH:18][CH:17]=[CH:16]4)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.O1CCCCC1[O:31][CH2:32][CH2:33][N:34]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[N:35]1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:24][C:14]1[C:13]([CH:11]([C:8]2[N:6]3[N:7]=[C:2]([C:37]4[CH:36]=[N:35][N:34]([CH2:33][CH2:32][OH:31])[CH:38]=4)[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)[CH3:12])=[C:22]([F:23])[CH:21]=[C:20]2[C:15]=1[CH:16]=[CH:17][CH:18]=[N:19]2

참가 물질

7

반응물 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 58147541(Rac)-6-[1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-5,7-difluoro-quinolineHCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

생성물 1

HCID 57917349(Rac)-2-(4-{3-[1-(5,7-difluoro-quinolin-6-yl)-ethyl]-imidazo[1,2-b]pyridazin-6-yl}-pyrazol-1-yl)ethanol

시약·촉매·용매 2

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 80711,2-Dimethoxyethane용매

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온도
150 °C

실험 절차

(rac)-6-[1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-5,7-difluoro-quinoline (Stage 182.1, 620 mg, 1.529 mmol) was dissolved in DME (5 mL) in a microwave reactor with 1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (Stage 171.4, 493 mg, 1.529 mmol) and a solution of 2 M Na2CO3 (2.75 mL). Then tetrakis(triphenylphosphine)-palladium (88 mg) was added and the RM was heated at 150° C. for 15 min under microwave irradiations. It was then taken up with EtOAc and washed with 10% Na2CO3 sol. and brine. The organic layer was dried over Na2SO4 and the solvent was removed. It was then dissolved in DCM (18 mL) and HCl in dioxane (4 N, 1.146 mL) was added. It was stirred at rt for 2 h. The solvent was removed and it was taken up in EtOAc/MeOH (9:1) and washed with water and brine. The organic layer was dried over Na2SO4 and the solvent was removed. The residue was triturated with Et2O and the solid was filtered off. The yellow solid obtained was the pure racemate of the title compound (tR 1.1 min (conditions 2), MH+=421)

후처리

  1. washwashed with 10% Na2CO3 sol. and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. customthe solvent was removed
  4. dissolutionIt was then dissolved in DCM (18 mL)
  5. additionHCl in dioxane (4 N, 1.146 mL) was added
  6. customThe solvent was removed
  7. washwashed with water and brine
  8. dry with materialThe organic layer was dried over Na2SO4
  9. customthe solvent was removed
  10. customThe residue was triturated with Et2O
  11. filtrationthe solid was filtered off
  12. customThe yellow solid obtained

출처 및 근거

ORD 기록
ord-7fd314cde442447d832db07e53715aea
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822468B2

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