Potassium Phosphate, Tribasic → (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[1-(2,2,2-trifluoroethyl)pyrrolidin-3-yl]phenyl]-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol

HRID 929243노트

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HRID 929243 반응식
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl:9][C:10]1[CH:11]=[C:12]2[N:19]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:18]([O:28][C@H:29]3[C@H:33]4[O:34][CH2:35][C@@H:36]([OH:37])[C@H:32]4[O:31][CH2:30]3)=[N:17][C:13]2=[N:14][C:15]=1I.CC1(C)C(C)(C)OB([C:46]2[CH:51]=[CH:50][C:49]([CH:52]3[CH2:56][CH2:55][N:54]([CH2:57][C:58]([F:61])([F:60])[F:59])[CH2:53]3)=[CH:48][CH:47]=2)O1>O1CCOCC1.C(Cl)Cl>[Cl:9][C:10]1[CH:11]=[C:12]2[N:19]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:18]([O:28][C@H:29]3[C@H:33]4[O:34][CH2:35][C@@H:36]([OH:37])[C@H:32]4[O:31][CH2:30]3)=[N:17][C:13]2=[N:14][C:15]=1[C:46]1[CH:47]=[CH:48][C:49]([CH:52]2[CH2:56][CH2:55][N:54]([CH2:57][C:58]([F:60])([F:59])[F:61])[CH2:53]2)=[CH:50][CH:51]=1

참가 물질

6

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 90042470(3R,3aR,6R,6aR)-6-((6-chloro-5-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-olHCID 900426383-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-(2,2,2-trifluoroethyl)pyrrolidine

생성물 1

HCID 131735111(3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[1-(2,2,2-trifluoroethyl)pyrrolidin-3-yl]phenyl]-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

Tripotassium phosphate 2.0 M aqueous solution (0.6 ml, 1.200 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (25.2 mg, 0.031 mmol) were added to a stirred solution of (3R,3aR,6R,6aR)-6-[6-chloro-5-iodo-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol (147.1 mg, 0.266 mmol) and 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-(2,2,2-trifluoroethyl)pyrrolidine (94.6 mg, 0.266 mmol) in dioxane (2.1 ml). The reaction mixture was degassed (3×) and placed under nitrogen before being heated to 80° C. After 18 hours, the reaction mixture was cooled to room temperature before being partitioned between EtOAc (50 ml) and water (50 ml). The aqueous layer was separated and extracted with EtOAc (2×50 ml). The organic layers were combined, washed with brine (1×30 ml), dried over MgSO4, filtered, and evaporated under reduced pressure to give a yellow residue. The residue was dissolved in DCM, loaded onto a 5 g silica solid load cartridge, and purified using an ISCO Rf and a 12 g silica column (CV=16.8 ml) by eluting as follows: 100% Hex (5 CV), 0-70% EtOAc/Hex gradient (50 CV), 70% EtOAc/Hex (35 CV) at 30 ml/min. The product fractions were combined and evaporated under reduced pressure to give the desired product as a yellow residue. LC-MS: calculated for C30H38ClF3N4O5Si 654.23 observed m/e: 655.32 (M+H)+ (Rt 1.37/2 min)

후처리

  1. customThe reaction mixture was degassed (3×)
  2. temperaturethe reaction mixture was cooled to room temperature
  3. custombefore being partitioned between EtOAc (50 ml) and water (50 ml)
  4. customThe aqueous layer was separated
  5. extractionextracted with EtOAc (2×50 ml)
  6. washwashed with brine (1×30 ml)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customto give a yellow residue
  11. custompurified
  12. washa 12 g silica column (CV=16.8 ml) by eluting
  13. customevaporated under reduced pressure

출처 및 근거

ORD 기록
ord-ee56a64fb94d425f8ba21f88494c6ace
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290517B2

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