Chloroacetone → (S)-1-(2-amino-2'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-7'-yloxy)propan-2-one

HRID 335772노트

반응식

HRID 335772 반응식
[NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([N:26]=1)[C:18]1[CH:17]=[C:16]([OH:19])[CH:15]=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)=[CH:9][CH:10]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:34][C:35]([CH3:37])=[O:36]>CN(C=O)C>[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([N:26]=1)[C:6]1[CH:7]=[C:8]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)[CH:9]=[CH:10][C:11]=1[O:12][C:13]1[C:18]2=[CH:17][C:16]([O:19][CH2:34][C:35](=[O:36])[CH3:37])=[CH:15][CH:14]=1

참가 물질

5

반응물 3

HCID 6571Chloroacetone3회HCID 10796Cesium carbonate2회HCID 58466221(S)-2-amino-7'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthen]-2'-ol

생성물 1

HCID 67243382(S)-1-(2-amino-2'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-7'-yloxy)propan-2-one

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A vial was charged with (S)-2-amino-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2′-ol (0.300 g, 0.869 mmol), cesium carbonate (0.425 g, 1.303 mmol). DMF (3.47 mL) was added, the vial was sonicated for 30 s, and the mixture was stirred vigorously for 20 min, at which time some white solid still remained. The vial was cooled in an ice-bath for 10 min, then 1-chloroacetone (0.083 mL, 1.042 mmol) was added dropwise and the reaction was stirred over the weekend, during which the bath warmed to RT. The reaction was cooled back to 0° C. and 1-chloroacetone (0.083 mL, 1.042 mmol) was added. The reaction was stirred for two hours before 0.5 equivalents of cesium carbonate and chloroacetone were added at one hour intervals until the reaction was complete. The mixture was partitioned between water and EtOAc. The layers were separated, and the aqueous layer was extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The material was purified via column chromatography (RediSep 40 g, gradient elution 0-5% MeOH:DCM) to afford (S)-1-(2-amino-2′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yloxy)propan-2-one as a white solid. The remaining fractions were combined and concentrated to afford impure material as an off-white solid.

후처리

  1. customthe vial was sonicated for 30 s
  2. temperatureThe vial was cooled in an ice-bath for 10 min
  3. stirringthe reaction was stirred over the weekend, during which the bath
  4. temperatureThe reaction was cooled back to 0° C.
  5. additionwere added at one hour intervals until the reaction
  6. customThe mixture was partitioned between water and EtOAc
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with EtOAc (2×)
  9. dry with materialThe combined organic extracts were dried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customThe material was purified via column chromatography (RediSep 40 g, gradient elution 0-5% MeOH:DCM)

출처 및 근거

ORD 기록
ord-45302ff389964eeeb808dcfbaed050b2
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08883782B2

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