Cesium carbonate → (S)-tert-butyl (1-((6-(2-methoxyethyl)-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

HRID 1398318ノート

反応式

HRID 1398318 の反応式
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[C:9](=[CH:10][N:11]=[CH:12][CH:13]=3)[C:8](=[O:15])[N:7]([CH:16]3[CH2:18]C3)[C:6]=2[CH:19]=1.[C:20](=O)([O-])[O-:21].[Cs+].[Cs+].[C:26]([NH:33][C@H:34]([CH2:39][OH:40])[CH2:35][CH:36]([CH3:38])[CH3:37])([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].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>[CH3:20][O:21][CH2:18][CH2:16][N:7]1[C:6]2[CH:19]=[C:2]([O:40][CH2:39][C@@H:34]([NH:33][C:26](=[O:27])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])[CH2:35][CH:36]([CH3:37])[CH3:38])[CH:3]=[CH:4][C:5]=2[C:14]2[C:9](=[CH:10][N:11]=[CH:12][CH:13]=2)[C:8]1=[O:15]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 7018766Boc-L-leucinolHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 867103158-chloro-6-cyclopropylbenzo[c][2,7]naphthyridin-5(6H)-one

生成物 1

HCID 86710324(S)-tert-butyl (1-((6-(2-methoxyethyl)-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate収率 49.1%

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 solution 8-chloro-6-cyclopropylbenzo[c][2,7]naphthyridin-5(6H)-one (100 mg, 0.346 mmol) in toluene (5 mL) at room temperature was added cesium carbonate (169 mg, 0.520 mmol) and N-Boc-L-leucinol (226 mg, 1.039 mmol) and the mixture was degassed with nitrogen for 5 min. The mixture was then treated with di-tert-butyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (47.8 mg, 0.208 mmol) followed by palladium(II)acetate (23.3 mg, 0.104 mmol) and degassed for another 10 min. The reaction mixture was sealed and heated at 80° C. After overnight stirring the reaction mixture was cooled to room temperature and filtered through diatomaceous earth (Celite®). The bed was washed with ethyl acetate (15 mL) and the filtrate was concentrated under reduced pressure to afford crude product which was purified by combi flash (gradient of ethyl acetate and petroleum ether) afford (S)-tert-butyl (1-((6-(2-methoxyethyl)-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (80 mg, 0.170 mmol, 49% yield) as a brown gum. LC/MS (ESI) m/e 470.3 [(M+H)+, calcd C26H36N3O5 470.3]; LC/MS retention time (method A): tR=2.02 min.

後処理

  1. customthe mixture was degassed with nitrogen for 5 min
  2. customdegassed for another 10 min
  3. customThe reaction mixture was sealed
  4. temperaturewas cooled to room temperature
  5. filtrationfiltered through diatomaceous earth (Celite®)
  6. washThe bed was washed with ethyl acetate (15 mL)
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customto afford crude product which
  9. customwas purified by combi flash (gradient of ethyl acetate and petroleum ether)

出典と根拠

ORDレコード
ord-79ba07c569274a618c20cf9357003465
出典データセット
uspto-grants-2014_12
特許番号
US08901305B2

反応ノート

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