Sodium Bicarbonate → HCID 90042151, compound

HRID 929152Notes

Reaction equation

HRID 929152 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[NH:22][C:21]([O:23][C@@H:24]3[CH2:28][O:27][C@@H:26]4[C:29](=[O:32])[CH2:30][O:31][C@H:25]34)=[N:20][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:9]=1.[CH:33]([Mg]Br)=[CH2:34].C([O-])(O)=O.[Na+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:22][C:21]([O:23][C@@H:24]3[CH2:28][O:27][C@@H:26]4[C@:29]([CH:33]=[CH2:34])([OH:32])[CH2:30][O:31][C@H:25]34)=[N:20][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 90041963HCID 90041963, compoundHCID 178418507HCID 178418507, compound

Product 1

HCID 90042151HCID 90042151, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A stirred suspension of (3R,3aR,6aS)-3-[[6-chloro-5-(4-phenylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,6a-tetrahydrofuro[3,2-b]furan-6-one (75.4 mg, 0.168 mmol) in THF (1.6 ml) was degassed (3×) and placed under nitrogen after being cooled to 0° C. in an ice bath. Vinylmagnesium bromide (1.6 ml, 1.600 mmol) was added to the reaction mixture slowly. The reaction mixture was stirred at 0° C. for 20 min, then at room temperature for 1.5 h. The reaction mixture was added via pipette to saturated aqueous NaHCO3 (20 ml) before being partitioned between EtOAc (40 ml) and water (20 ml). The aqueous layer was extracted with EtOAc (2×20 ml). The organic layers were combined, washed with brine (1×20 ml), dried over MgSO4, filtered, and evaporated under reduced pressure to give a yellow residue. This material was purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-100% acetonitrile/water+0.05% TFA gradient, followed by a 100% acetonitrile+0.05% TFA. The product fractions were combined, evaporated under reduced pressure, and lyophilized from ethanol and benzene to give the title compound as a white solid. LC-MS: calculated for C26H22ClN3O4 475.13 observed m/e: 476.18 (M+H)+ (Rt 1.21/2 min).

Workup

  1. customwas degassed (3×)
  2. waitat room temperature for 1.5 h
  3. custombefore being partitioned between EtOAc (40 ml) and water (20 ml)
  4. extractionThe aqueous layer was extracted with EtOAc (2×20 ml)
  5. washwashed with brine (1×20 ml)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto give a yellow residue
  10. customThis material was purified by preparative HPLC reverse phase (C-18)
  11. washeluting with a 20%-100% acetonitrile/water+0.05% TFA gradient
  12. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-4bd4cb3fcc1541499349b6485aaf2061
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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