Methanol → (2S,3S)-2-[(R)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2,5-dioxo-imidazolidin-1-yl]-N-[4-(1-hydroxy-propyl)-thiazol-2-yl]-3-phenyl-butyramide

HRID 32846

반응식

HRID 32846 반응식
C(C1N=C([N:9]([C:38]2[S:39][CH:40]=[C:41]([C:43](=[O:46])[CH2:44][CH3:45])[N:42]=2)[C:10](=[O:37])[C@@H:11]([N:20]2[C:24](=[O:25])[C@@H:23]([C:26]3[CH:35]=[CH:34][C:29]4[O:30][CH2:31][CH2:32][O:33][C:28]=4[CH:27]=3)[NH:22][C:21]2=[O:36])[C@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:13])SC=1)(=O)C.CO.[BH4-].[Na+].P([O-])([O-])(O)=O.[K+].[K+]>[Cl-].[Na+].O>[O:30]1[C:29]2[CH:34]=[CH:35][C:26]([C@@H:23]3[C:24](=[O:25])[N:20]([C@@H:11]([C@H:12]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH3:13])[C:10]([NH:9][C:38]4[S:39][CH:40]=[C:41]([CH:43]([OH:46])[CH2:44][CH3:45])[N:42]=4)=[O:37])[C:21](=[O:36])[NH:22]3)=[CH:27][C:28]=2[O:33][CH2:32][CH2:31]1

참가 물질

6

반응물 4

HCID 887MethanolHCID 24450Potassium Phosphate, DibasicHCID 4311764Sodium borohydride2회HCID 69143984(2S,3S)-N-(4-Acetyl-thiazol-2-yl)-2-[(R)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide

생성물 1

HCID 58604317(2S,3S)-2-[(R)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2,5-dioxo-imidazolidin-1-yl]-N-[4-(1-hydroxy-propyl)-thiazol-2-yl]-3-phenyl-butyramide수율 73%

시약·촉매·용매 1

HCID 57417360Sodium chloride; water용매

반응 조건

온도
5 °C

실험 절차

(2S,3S)-N-(4-Acetyl-thiazol-2-yl)-2-[(R)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide (from example 5a) (20 mg, 0.037 mmol) was dissolved in warm dry methanol (5 mL). The reaction mixture was then cooled in an ice bath and sodium borohydride (1.56 mg, 0.041 mmol) was added. The reaction was stirred at 5° C. for 30 minutes, additional sodium borohydride (1.56 mg, 0.041 mmol) was added and stirring continued for 1 hour. The clear solution was treated with 1.5 N aqueous potassium hydrogen phosphate (1 mL) and the cloudy mixture was stirred for a few minutes, then diluted with saturated brine and extracted with ethyl acetate (3×25 mL). The combined organic extracts were washed with saturated brine, dried over sodium sulfate and concentrated in vacuo. The pale yellow residue was taken into a small amount of dichloromethane (0.5 ml) then treated with diethyl ether (2 mL) and this turbid solution was further precipitated with of hexanes (3 mL). The mixture was stirred for 5 minutes then filtered over a 1.7 cm funnel, washed with hexanes and air dried to give (2S,3S)-2-[(R)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2,5-dioxo-imidazolidin-1-yl]-N-[4-(1-hydroxy-propyl)-thiazol-2-yl]-3-phenyl-butyramide as a white solid (14.5 mg, 73%).

후처리

  1. temperatureThe reaction mixture was then cooled in an ice bath
  2. stirringstirring
  3. waitcontinued for 1 hour
  4. stirringthe cloudy mixture was stirred for a few minutes
  5. extractionextracted with ethyl acetate (3×25 mL)
  6. washThe combined organic extracts were washed with saturated brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. additionthen treated with diethyl ether (2 mL)
  10. customthis turbid solution was further precipitated with of hexanes (3 mL)
  11. stirringThe mixture was stirred for 5 minutes
  12. filtrationthen filtered over a 1.7 cm funnel
  13. washwashed with hexanes and air
  14. customdried

출처 및 근거

ORD 기록
ord-25d646505d3e43c6b649b7aa94bde9b8
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07427635B2

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