Cesium carbonate → (S)-2,2-Difluoro-2-(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)-1-(2-(5-((pyridazin-4-yloxy)methyl)isoxazol-3-yl)pyrrolidin-1-yl)ethanone

HRID 710068

반응식

HRID 710068 반응식
[F:1][C:2]([F:28])([C:17]1([OH:27])[CH2:22][C:21]([CH3:24])([CH3:23])[CH2:20][C:19]([CH3:26])([CH3:25])[CH2:18]1)[C:3]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[CH:14]=[C:13]([CH2:15][OH:16])[O:12][N:11]=1)=[O:4].Br.Br[C:31]1[CH:36]=[CH:35][N:34]=[N:33][CH:32]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1(C2C3C(=CC=CC=3)C=CC=2)C2C(=CC=CC=2)C=CC=1P(C(C)(C)C)C(C)(C)C>CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1>[F:28][C:2]([F:1])([C:17]1([OH:27])[CH2:18][C:19]([CH3:26])([CH3:25])[CH2:20][C:21]([CH3:24])([CH3:23])[CH2:22]1)[C:3]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[CH:14]=[C:13]([CH2:15][O:16][C:31]2[CH:36]=[CH:35][N:34]=[N:33][CH:32]=2)[O:12][N:11]=1)=[O:4]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 534079064-Bromopyridazine hydrobromideHCID 86706747(S)-2,2-Difluoro-2-(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)-1-(2-(5-(hydroxymethyl)isoxazol-3-yl)pyrrolidin-1-yl)ethanone

생성물 1

HCID 86706781(S)-2,2-Difluoro-2-(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)-1-(2-(5-((pyridazin-4-yloxy)methyl)isoxazol-3-yl)pyrrolidin-1-yl)ethanone수율 16.7%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

반응 조건

온도
100 °C

실험 절차

A sealed tube was charged with a mixture prepared by adding toluene (2 ml) to Compound 18 (30 mg), 4-bromopyridazine hydrobromide (22 mg), Pd(OAc)2 (2 mg), Cs2CO3 (37 mg), and [1,1′-binaphthalen]-2-yldi-tert-butylphosphine (3 mg) and the mixture was stirred at 100° C. for 4 hours. After cooling the reaction mixture to room temperature, NH silica gel was added, followed by stirring for a while. After separating the silica gel by filtration, the silica gel was washed with chloroform and the solvent was distilled off; the resulting residue was purified by reverse-phase preparative HPLC to give the titled compound (6.0 mg, colorless oil.)

후처리

  1. additionA sealed tube was charged with a mixture
  2. customprepared
  3. temperatureAfter cooling the reaction mixture to room temperature
  4. additionNH silica gel was added
  5. stirringby stirring for a while
  6. customAfter separating the silica gel
  7. filtrationby filtration
  8. washthe silica gel was washed with chloroform
  9. distillationthe solvent was distilled off
  10. customthe resulting residue was purified by reverse-phase preparative HPLC

출처 및 근거

ORD 기록
ord-a77022a34471403ea39f5d751aafaa39
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181229B2

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