(Dimethyl sulfide)trihydroboron → (1R)-1-[6-(2,5-dimethyl-1H-pyrrol-1-yl)-3-pyridinyl]-2-({[(2R)-6-iodo-3,4-dihydro-2H-chromen-2-yl]methyl}amino)ethanol

HRID 896896ノート

反応式

HRID 896896 の反応式
[CH3:1][C:2]1[N:3]([C:8]2[N:13]=[CH:12][C:11]([C@@H:14]([OH:30])[CH2:15][NH:16][C:17]([C@H:19]3[CH2:28][CH2:27][C:26]4[C:21](=[CH:22][CH:23]=[C:24]([I:29])[CH:25]=4)[O:20]3)=O)=[CH:10][CH:9]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.B.CSC>C1COCC1>[CH3:1][C:2]1[N:3]([C:8]2[N:13]=[CH:12][C:11]([C@@H:14]([OH:30])[CH2:15][NH:16][CH2:17][C@H:19]3[CH2:28][CH2:27][C:26]4[C:21](=[CH:22][CH:23]=[C:24]([I:29])[CH:25]=4)[O:20]3)=[CH:10][CH:9]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1

参加物

4

反応物 2

HCID 12423031(Dimethyl sulfide)trihydroboronHCID 59118220(2R)-N-{(2R)-2-[6-(2,5-dimethyl-1H-pyrrol-1-yl)-3-pyridinyl]-2-hydroxyethyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide

生成物 1

HCID 59118192(1R)-1-[6-(2,5-dimethyl-1H-pyrrol-1-yl)-3-pyridinyl]-2-({[(2R)-6-iodo-3,4-dihydro-2H-chromen-2-yl]methyl}amino)ethanol収率 63%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of (2R)-N-{(2R)-2-[6-(2,5-dimethyl-1H-pyrrol-1-yl)-3-pyridinyl]-2-hydroxyethyl}-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide (Example 355, 7.67 mmol, 1 eq.) in THF (150 mL) at room temperature was added slowly borane-methyl sulfide complex (2M in THF, 38.4 mmol, 5.0 eq.). After completion of the addition, the reaction mixture was heated to reflux for 2 hours and was then cooled to room temperature. The excess borane was quenched by the dropwise addition of EtOH (9 mL) followed by the slow addition of 2 M HCl (40 mL). The resulting mixture was heated to reflux for 1 hour and was then allow to cool to room temperature. The mixture was basified with 1N NaOH and extracted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous sodium sulfate, concentrated, and purified by medium pressure column chromatography (Biotage 40S normal phase silica gel column, using a gradient of 1:4 hexanes:EtOAc to 1:10 MeOH:EtOAc). The product was obtained as a pale yellow oil in 63% yield. MH+=503.9, RT=3.23 min.

後処理

  1. additionAfter completion of the addition
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux for 2 hours
  4. customThe excess borane was quenched by the dropwise addition of EtOH (9 mL)
  5. additionfollowed by the slow addition of 2 M HCl (40 mL)
  6. temperatureThe resulting mixture was heated
  7. temperatureto reflux for 1 hour
  8. temperatureto cool to room temperature
  9. extractionextracted with ethyl acetate
  10. extractionThe organic extract
  11. washwas washed with brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. concentrationconcentrated
  14. custompurified by medium pressure column chromatography (Biotage 40S normal phase silica gel column
  15. customThe product was obtained as a pale yellow oil in 63% yield

出典と根拠

ORDレコード
ord-2023d4a7fd704e31b9a9b37a9750262f
出典データセット
uspto-grants-2005_07
特許番号
US06919371B2

反応ノート

読み込み中…