Potassium Phosphate, Tribasic → Methyl 4'-(6-chloro-2-(((4aR,7R,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-yl)oxy)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-5-yl)-[1,1'-biphenyl]-4-carboxylate

HRID 1050243노트

반응식

HRID 1050243 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[N:14]=[C:15]([O:25][C@H:26]4[CH2:35][O:34][C@H:33]5[C@@H:28]([O:29][CH:30]([C:36]6[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=6)[O:31][CH2:32]5)[CH2:27]4)[N:16]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:11]3=[CH:10][C:9]=2[Cl:42])=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.CC1(C)C(C)(C)OB([C:80]2[CH:89]=[CH:88][C:83]([C:84]([O:86][CH3:87])=[O:85])=[CH:82][CH:81]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[Cl:42][C:9]1[CH:10]=[C:11]2[N:16]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:22])([CH3:23])[CH3:24])[C:15]([O:25][C@H:26]3[CH2:35][O:34][C@H:33]4[C@@H:28]([O:29][CH:30]([C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)[O:31][CH2:32]4)[CH2:27]3)=[N:14][C:12]2=[N:13][C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([C:80]2[CH:89]=[CH:88][C:83]([C:84]([O:86][CH3:87])=[O:85])=[CH:82][CH:81]=2)=[CH:3][CH:4]=1

참가 물질

7

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 2773500Methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 900448115-(4-bromophenyl)-6-chloro-2-(((4aR,7R,8aS)-2-phenylhexahydropyrano-[3,2-d][1,3]dioxin-7-yl)oxy)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine

생성물 1

HCID 131736056Methyl 4'-(6-chloro-2-(((4aR,7R,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-yl)oxy)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-5-yl)-[1,1'-biphenyl]-4-carboxylate

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 962Water용매

반응 조건

온도
100 °C

실험 절차

To a stirred solution of 5-(4-bromophenyl)-6-chloro-2-(((4aR,7R,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-yl)oxy)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine (586 mg, 0.871 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (36 mg, 0.088 mmol), methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (297 mg, 1.132 mmol), and tribasic potassium phosphate (554 mg, 2.61 mmol) in tolune (2 mL) and water (0.1 mL) under nitrogen was added palladium acetate (10 mg, 0.045 mmol). The mixture was stirred at 100° C. for 16 hours, then allowed to cool to room temperature. The mixture was filtered, concentrated under reduced pressure, and chromatographed using a Biotage™ 50 g silica gel cartridge eluted with 0-30% EtOAc in 1:1 Hexane/DCM over 30 column volumes. The product fractions were concentrated under reduced pressure to provide the desired product as a foamy off-white solid. LC-MS: calculated for C39H42ClN3O7Si 727.25, observed m/e: 728.33 (M+H)+ (Rt 3.11/4 min).

후처리

  1. temperatureto cool to room temperature
  2. filtrationThe mixture was filtered
  3. concentrationconcentrated under reduced pressure
  4. customchromatographed
  5. washeluted with 0-30% EtOAc in 1:1 Hexane/DCM over 30 column volumes
  6. concentrationThe product fractions were concentrated under reduced pressure

출처 및 근거

ORD 기록
ord-7658951755144f79a9aa0182d3a59d8d
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382243B2

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