Cesium carbonate → 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

HRID 1050232Notes

Reaction equation

HRID 1050232 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[N:14]=[C:15](S(C)(=O)=O)[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:29])=[CH:4][CH:3]=1.[C:30]1([CH:36]2[O:41][C@H:40]3[CH2:42][C@@H:43]([OH:46])[CH2:44][O:45][C@@H:39]3[CH2:38][O:37]2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[N:14]=[C:15]([O:46][C@H:43]4[CH2:44][O:45][C@H:39]5[C@@H:40]([O:41][CH:36]([C:30]6[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=6)[O:37][CH2:38]5)[CH2:42]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:29])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 217656031,5-Anhydro-4,6-O-benzylidene-3-deoxy-D-glucitolHCID 895581002-[[5-(4-Bromophenyl)-6-chloro-2-methylsulfonyl-imidazo[4,5-b]pyridin-1-yl]methoxy]ethyl-trimethyl-silane

Product 1

HCID 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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-(4-bromophenyl)-6-chloro-2-(methylsulfonyl)-1-((2-(trimethylsilyl)-ethoxy)methyl)-1H-imidazo[4,5-b]pyridine (2.6 g, 5.03 mmol), (4aR,7R,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-ol (1.307 g, 5.53 mmol), and cesium carbonate (4.92 g, 15.09 mmol) were dissolved in DMF (25.1 mL). The reaction mixture was stirred overnight at rt, then diluted with EtOAc and saturated NH4C/water (50:50). The aqueous phase was extracted with EtOAc (×2) and the combined extracts were washed with sat. NaHCO3 and brine, then dried over Na2SO4, filtered, and concentrated. The resulting residue was purified by column chromatography on a Biotage™ 100 g column by eluting with 10% EtOAc:Hexane to 70% EtOAc:Hexane to yield the desired product. LC-MS: calculated for C31H35BrClN3O5Si 671.12 observed m/e: 671.83 (M+H)+ (Rt 1.37/2 min).

Workup

  1. extractionThe aqueous phase was extracted with EtOAc (×2)
  2. washthe combined extracts were washed with sat. NaHCO3 and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by column chromatography on a Biotage™ 100 g column
  7. washby eluting with 10% EtOAc

Sources & evidence

ORD record
ord-43e9f9c1c6734b2e87ca279ae7dbd440
Source dataset
uspto-grants-2016_07
Patent number
US09382243B2

Reaction notes

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