Triethylamine → HCID 131736059, compound

HRID 1050267Notes

Reaction equation

HRID 1050267 reaction equation
[C:1]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:6]=[CH:5][C:4]([C:7]2[N:12]=[C:11]3[N:13]=[C:14]([O:16][C@H:17]4[CH2:22][O:21][C@H:20]([CH2:23][OH:24])[C@@H:19]([OH:25])[CH2:18]4)[NH:15][C:10]3=[CH:9][C:8]=2[Cl:26])=[CH:3][CH:2]=1.C(N([CH2:38][CH3:39])CC)C.[Si:40](Cl)([CH2:45][CH3:46])([CH2:43][CH3:44])[CH2:41][CH3:42].C(=O)(O)[O-].[Na+].[CH3:53][Si:54]([CH2:57][CH2:58][O:59][CH2:60]Cl)([CH3:56])[CH3:55]>CN(C=O)C>[C:1]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:2]=[CH:3][C:4]([C:7]2[N:12]=[C:11]3[N:13]=[C:14]([O:16][C@@H:17]4[CH2:18][C@H:19]([O:25][Si:40]([CH2:45][CH3:46])([CH2:43][CH3:44])[CH2:41][CH3:42])[C@@H:20]([CH2:23][O:24][Si:40]([CH2:38][CH3:39])([CH2:43][CH3:44])[CH2:41][CH3:42])[O:21][CH2:22]4)[N:15]([CH2:60][O:59][CH2:58][CH2:57][Si:54]([CH3:56])([CH3:55])[CH3:53])[C:10]3=[CH:9][C:8]=2[Cl:26])=[CH:5][CH:6]=1

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 13819ChlorotriethylsilaneHCID 516892Sodium Bicarbonate2×HCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 89558025HCID 89558025, compound

Product 1

HCID 131736059HCID 131736059, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (2R,3S,5R)-5-((5-([1,1′-biphenyl]-4-yl)-6-chloro-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol (256 mg, 0.566 mmol) and triethylamine (0.40 mL, 287 mg, 2.83 mmol) in anhydrous DMF (3.0 mL) under nitrogen at 0° C. was added TESCl (0.38 mL, 342 mg, 2.266 mmol), dropwise over 1 minute. The mixture was allowed to stir at room temperature for 2.5 hours, then poured into saturated aqueous sodium bicarbonate (40 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (40 mL), dried over sodium sulfate, and concentrated under reduced pressure. After drying under high vacuum for 1 hour, the resultant clear oil was dissolved in anhydrous DMF (3.0 mL). To this solution was added triethylamine (0.16 mL, 115 mg, 1.133 mmol) and SEMCl (0.12 mL, 113 mg, 0.680 mmol). After stirring at room temperature for 30 minutes, the mixture was poured into saturated aqueous sodium bicarbonate (40 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (40 mL), dried over sodium sulfate, and concentrated under reduced pressure to provide the desired product as a yellow oil. LC-MS: calculated for C42H64ClN3O5Si3 809.38, observed m/e: 810.46 (M+H)+ (Rt 3.80/4 min).

Workup

  1. extractionextracted with EtOAc (2×50 mL)
  2. washThe combined organic layers were washed with brine (40 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customAfter drying under high vacuum for 1 hour
  6. dissolutionthe resultant clear oil was dissolved in anhydrous DMF (3.0 mL)
  7. stirringAfter stirring at room temperature for 30 minutes
  8. extractionextracted with EtOAc (2×50 mL)
  9. washThe combined organic layers were washed with brine (40 mL)
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-807313650c8545ce9189cf7a4871b298
Source dataset
uspto-grants-2016_07
Patent number
US09382243B2

Reaction notes

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