Cesium carbonate → N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy]-4-pyrimidinyl]-1-azetidinesulfonamide

HRID 1024911노트

반응식

HRID 1024911 반응식
[N:1]1([S:5]([NH2:8])(=[O:7])=[O:6])[CH2:4][CH2:3][CH2:2]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].ClC1C=C(OC2COC(C3C=CC=CC=3)OC2)N=C(SCC2C=CC=C(F)C=2F)N=1.Cl[C:80]1[CH:85]=[C:84]([O:86][C@@H:87]([C@@H:89]2[CH2:93][O:92][C:91]([CH3:95])([CH3:94])[O:90]2)[CH3:88])[N:83]=[C:82]([S:96][CH2:97][C:98]2[CH:103]=[CH:102][CH:101]=[C:100]([F:104])[C:99]=2[F:105])[N:81]=1.[Cl-].[NH4+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:105][C:99]1[C:100]([F:104])=[CH:101][CH:102]=[CH:103][C:98]=1[CH2:97][S:96][C:82]1[N:81]=[C:80]([NH:8][S:5]([N:1]2[CH2:4][CH2:3][CH2:2]2)(=[O:7])=[O:6])[CH:85]=[C:84]([O:86][C@@H:87]([C@@H:89]2[CH2:93][O:92][C:91]([CH3:94])([CH3:95])[O:90]2)[CH3:88])[N:83]=1

참가 물질

9

반응물 6

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 450805661-AzetidinesulfonamideHCID 536283394-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-pyrimidineHCID 86619881HCID 86619881, 화합물

생성물 1

HCID 53628361N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy]-4-pyrimidinyl]-1-azetidinesulfonamide

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

A mixture of azetidine-1-sulphonamide (prepared according to patent WO 2004/011443, 0.16 g), tris(dibenzylideneacetone)-dipalladium (0) (33 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (17 mg), cesium carbonate (0.28 g) and 4-chloro-2-[[(2,3-difluorophenyl)-methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-pyrimidine (the product of step i) (0.25 g) in dioxane (10 mL) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 20 min. Saturated ammonium chloride was added and the resulting mixture extracted with EtOAc. The combined organic extracts were washed with saturated aqueous sodium chloride, dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography on silica gel using EtOAc/isohexane (3:7) as eluent to give the subtitle compound as a yellow oil. Yield: 0.13 g.

후처리

  1. temperaturewas heated
  2. temperature300 W, open vessel with cooling for 20 min
  3. extractionthe resulting mixture extracted with EtOAc
  4. washThe combined organic extracts were washed with saturated aqueous sodium chloride
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography on silica gel

출처 및 근거

ORD 기록
ord-17d46ca2820a461bbe6835f29ae8aec6
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08722883B2

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