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

HRID 870906ノート

反応式

HRID 870906 の反応式
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.[OH:19][CH2:20][C@@H:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:22][CH:23]([CH3:25])[CH3:24].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:29]([O:28][C:27](=[O:33])[NH:26][C@@H:21]([CH2:22][CH:23]([CH3:24])[CH3:25])[CH2:20][O:19][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)([CH3:32])([CH3:31])[CH3:30]

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 7018766Boc-L-leucinolHCID 866958998-chloro-5-cyclopropyl-5H-chromeno[3,4-c]pyridine

生成物 1

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

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-45decf8e05e84430a2cf073aeaea083f
出典データセット
uspto-grants-2015_03
特許番号
US08969564B2

反応ノート

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