Acetonitrile → 5-bromo-3-(2-difluoromethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine

HRID 2388952노트

반응식

HRID 2388952 반응식
[F:1][CH:2]([F:19])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1B1OC(C)(C)C(C)(C)O1.[Br:20][C:21]1[CH:22]=[C:23]2[C:29](I)=[N:28][N:27]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:24]2=[N:25][CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+].C(#N)C>C1COCC1>[Br:20][C:21]1[CH:22]=[C:23]2[C:29]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[O:3][CH:2]([F:1])[F:19])=[N:28][N:27]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:24]2=[N:25][CH:26]=1

참가 물질

6

반응물 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 532167682-(2-(Difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 598361345-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine

생성물 1

HCID 579758295-bromo-3-(2-difluoromethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine수율 97.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
60 °C

실험 절차

2-(2-difluoromethoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (208 mg, 0.77 mmol), 5-bromo-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (350 mg, 0.77 mmol), 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichloromethane adduct (28 mg, 0.035 mmol) and aqueous solution of sodium carbonate (2 M, 0.77 mL) were suspended in anhydrous THF (7 mL) and acetonitrile (7 mL) under an atmosphere of nitrogen. The mixture was stirred at 60° C. for 12 h. The cooled mixture was applied to a Varian Chemelut cartridge and eluted with ethyl acetate. Purification by flash silica gel chromatography using a gradient of ethyl acetate and hexanes afforded 355 mg (0.75 mmol, 95%) of 5-bromo-3-(2-difluoromethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine as a white solid. MS: m/z 471 [MH+] which was directly used in the next step.

후처리

  1. washeluted with ethyl acetate
  2. customPurification by flash silica gel chromatography

출처 및 근거

ORD 기록
ord-b21e257da5f74ec5a552c3ab5d74e0ff
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08268994B2

반응 노트

불러오는 중…