Cesium carbonate → tert-butyl((2S)-1-((5-cyclopropyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

HRID 2369496노트

반응식

HRID 2369496 반응식
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:15]3[C:10](=[CH:11][N:12]=[CH:13][CH:14]=3)[CH:9]([CH:16]3[CH2:18][CH2:17]3)[O:8][C:6]=2[CH:7]=1.[C:19]([O:23][C:24](=[O:33])[NH:25][C@@H:26]([CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:27][OH:28])([CH3:22])([CH3:21])[CH3:20].C(=O)([O-])[O-].[Cs+].[Cs+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:19]([O:23][C:24](=[O:33])[NH:25][C@@H:26]([CH2:29][CH:30]([CH3:31])[CH3:32])[CH2:27][O:28][C:2]1[CH:3]=[CH:4][C:5]2[C:15]3[C:10](=[CH:11][N:12]=[CH:13][CH:14]=3)[CH:9]([CH:16]3[CH2:18][CH2:17]3)[O:8][C:6]=2[CH:7]=1)([CH3:22])([CH3:21])[CH3:20]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 7018766Boc-L-leucinolHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 866958998-chloro-5-cyclopropyl-5H-chromeno[3,4-c]pyridine

생성물 1

HCID 86724427tert-butyl((2S)-1-((5-cyclopropyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate수율 53.4%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

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온도
80 °C

실험 절차

To a stirred solution of 8-chloro-5-cyclopropyl-5H-chromeno[3,4-c]pyridine (275 mg, 1.067 mmol) in toluene (3 mL) was added (S)-tert-butyl(1-hydroxy-4-methylpentan-2-yl)carbamate (696 mg, 3.20 mmol), cesium carbonate (427 mg, 1.310 mmol), di-tert-butyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (272 mg, 0.640 mmol) and palladium (II) acetate (71.9 mg, 0.320 mmol). Nitrogen was bubbled through the reaction mixture for 10 min then the mixture was heated at 80° C. for 12 h. The reaction mixture was cooled to room temperature and filtered through celite. The filtrate was diluted with water (10 mL) and extracted with ethyl acetate (3×15 mL). The combined organic extracts were washed with brine (1×15 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified via silica gel chromatography (ethyl acetate/pet ether) to give tert-butyl-(2S)-1-(5-cyclopropyl-5H-chromeno[3,4-c]pyridin-8-yloxy)-4-methylpentan-2-ylcarbamate (250 mg, 0.57 mmol, 50% yield). LCMS (ESI) m/e 439.2 [(M+H)+, calcd for C26H35N2O4 439.3]; LC/MS retention time (Method C): tR=2.16 min.

후처리

  1. customNitrogen was bubbled through the reaction mixture for 10 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered through celite
  4. additionThe filtrate was diluted with water (10 mL)
  5. extractionextracted with ethyl acetate (3×15 mL)
  6. washThe combined organic extracts were washed with brine (1×15 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified via silica gel chromatography (ethyl acetate/pet ether)

출처 및 근거

ORD 기록
ord-05e718f281844c4db5a013c2ad9a3504
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08703953B2

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