Triethylamine → HCID 131736058, compound

HRID 1050266Notes

Reaction equation

HRID 1050266 reaction equation
[C:1]1([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:6]=[CH:5][C:4]([C:7]2[N:12]=[C:11]3[N:13]=[C:14]([O:24][C@H:25]4[CH2:30][O:29][C@H:28]([CH2:31][OH:32])[C@@H:27]([OH:33])[CH2:26]4)[N:15]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:10]3=[CH:9][C:8]=2[Cl:34])=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH3:48][C:49]([Si:52](Cl)([CH3:54])[CH3:53])([CH3:51])[CH3:50].C(=O)(O)[O-].[Na+]>CN(C=O)C.CN(C1C=CN=CC=1)C.C(Cl)Cl.CO>[C:1]1([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:6]=[CH:5][C:4]([C:7]2[N:12]=[C:11]3[N:13]=[C:14]([O:24][C@H:25]4[CH2:30][O:29][C@H:28]([CH2:31][O:32][Si:52]([C:49]([CH3:51])([CH3:50])[CH3:48])([CH3:54])[CH3:53])[C@@H:27]([OH:33])[CH2:26]4)[N:15]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:21])[CH3:22])[C:10]3=[CH:9][C:8]=2[Cl:34])=[CH:3][CH:2]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 28928tert-Butyldimethylsilyl chlorideHCID 516892Sodium BicarbonateHCID 131736057HCID 131736057, compound

Product 1

HCID 131736058HCID 131736058, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (2R,3S,5R)-5-((5-([1,1′-biphenyl]-4-yl)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol (242 mg, 0.416 mmol) in anhydrous DMF (2.0 mL) under nitrogen was added DMAP (10 mg, 0.083 mmol) and triethylamine (0.13 mL, 93 mg, 0.915 mmol). The mixture was cooled to 0° C., then TBSCl (132 mg, 0.873 mmol) was added as a solution in anhydrous DCM (0.5 mL). After stirring at 0° C. for 0.5 hours, methanol (5 mL) was added and the mixture was poured into saturated aqueous sodium bicarbonate (75 mL). The mixture was extracted with ethyl acetate (2×100 mL), and the combined organic layers were washed with brine (50 mL), dried over sodium sulfate, and concentrated under reduced pressure. The resultant oil was chromatographed using a Biotage™ 10 g silica gel cartridge eluted with 0-20% EtOAc in 1:1 Hexane/DCM over 20 column volumes. The combined product fractions were concentrated under reduced pressure and dried under high vacuum overnight to provide the desired product as a white solid film. LC-MS: calculated for C36H50ClN3O5Si2 695.30, observed m/e: 696.39 (M+H)+ (Rt 3.33/4 min).

Workup

  1. extractionThe mixture was extracted with ethyl acetate (2×100 mL)
  2. washthe combined organic layers were washed with brine (50 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resultant oil was chromatographed
  6. washeluted with 0-20% EtOAc in 1:1 Hexane/DCM over 20 column volumes
  7. concentrationThe combined product fractions were concentrated under reduced pressure
  8. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-09ed25f9736b46e6b8e3ad666eb452f9
Source dataset
uspto-grants-2016_07
Patent number
US09382243B2

Reaction notes

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