2,2'-(1,4-Phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) → 6-chloro-2-(((4aR,7R,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-yl)oxy)-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine

HRID 1050252Notes

Reaction equation

HRID 1050252 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[N:11]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:10]([O:20][C@H:21]3[CH2:30][O:29][C@H:28]4[C@@H:23]([O:24][CH:25]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)[O:26][CH2:27]4)[CH2:22]3)=[N:9][C:5]2=[N:6][C:7]=1I.[B:37]1([C:46]2[CH:51]=[CH:50][C:49](B3OC(C)(C)C(C)(C)O3)=[CH:48][CH:47]=2)[O:41][C:40]([CH3:43])([CH3:42])[C:39]([CH3:45])([CH3:44])[O:38]1>C1COCC1.CCOC(C)=O.C(=O)([O-])[O-].[Ag+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[N:11]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:10]([O:20][C@H:21]3[CH2:30][O:29][C@H:28]4[C@@H:23]([O:24][CH:25]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)[O:26][CH2:27]4)[CH2:22]3)=[N:9][C:5]2=[N:6][C:7]=1[C:49]1[CH:50]=[CH:51][C:46]([B:37]2[O:41][C:40]([CH3:43])([CH3:42])[C:39]([CH3:45])([CH3:44])[O:38]2)=[CH:47][CH:48]=1

Participants

7

Reactant 2

HCID 105924952,2'-(1,4-Phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)HCID 1234895916-chloro-5-iodo-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-

Product 1

HCID 900448896-chloro-2-(((4aR,7R,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-yl)oxy)-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 178418647HCID 178418647, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of 6-chloro-5-iodo-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 (4.29 g, 9.31 mmol) under nitrogen in anhydrous THF (30 mL) was added silver carbonate (3.08 g, 11.18 mmol), Pd(PPh3)4 (538 mg, 0.466 mmol), and 1,4-benzenediboronic acid bis(pinacol) ester (9.22 g, 27.9 mmol). The mixture was cooled to −78° C., a hard vacuum was pulled, and nitrogen was introduced (3×). The mixture was allowed to warm to room temperature, then heated to reflux. After 21 hours, the mixture was cooled to room temperature and diluted with EtOAc (80 mL). The mixture was filtered through celite with EtOAc rinse until filtrate was colorless. The filtrate was concentrated under reduced pressure. The resultant residue was chromatographed using a Biotage™ 150 g (100 g+50 g in series) silica gel cartridge eluted with 0-30% EtOAc in 1:1 Hexane/DCM over 15 column volumes. The product fractions were combined and concentrated under reduced pressure, then the resultant oil was dissolved in MeCN and water, frozen at −78° C., and lyophilized to dryness to provide the title compound as a yellow solid. LC-MS: calculated for C37H47BClN3O7Si 719.30, observed m/e: 720.43 (M+H)+ (Rt 3.25/4 min).

Workup

  1. additionnitrogen was introduced (3×)
  2. temperatureto warm to room temperature
  3. temperatureheated to reflux
  4. temperaturethe mixture was cooled to room temperature
  5. filtrationThe mixture was filtered through celite with EtOAc
  6. washrinse until filtrate
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customThe resultant residue was chromatographed
  9. washeluted with 0-30% EtOAc in 1:1 Hexane/DCM over 15 column volumes
  10. concentrationconcentrated under reduced pressure
  11. dissolutionthe resultant oil was dissolved in MeCN
  12. temperaturewater, frozen at −78° C.

Sources & evidence

ORD record
ord-e8db78e6a1fe467693b1a37d09f23bdb
Source dataset
uspto-grants-2016_07
Patent number
US09382243B2

Reaction notes

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