Pyridine → HCID 9900648, compound

HRID 2183552Notes

Reaction equation

HRID 2183552 reaction equation
[CH:1]1([Mg]Cl)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH4+:9].[Cl-].[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13]C=1.Cl[C:18]([O:20][CH2:21][CH3:22])=[O:19].[C:23]([OH:29])(C(F)(F)F)=O.C([O-])(O)=O.[Na+].C[C:36]#[N:37]>C1COCC1.C(Cl)Cl.CCOC(C)=O.O>[C:36]([C:15]1[CH:16]([CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[N:11]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:23](=[O:29])[NH:9][C:14]=1[CH3:13])#[N:37]

Participants

12

Reactant 7

HCID 1049PyridineHCID 6342AcetonitrileHCID 6422Trifluoroacetic acidHCID 10928Ethyl chloroformateHCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 178478990HCID 178478990, compound

Product 1

HCID 9900648HCID 9900648, compoundYield 60%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of the compound of Example 16, Step 2 (30 mg, 0.2 mmol) in THF (1.2 ml) was added cyclohexylmagnesium chloride (2 M in ether, 1.0 ml, 2 mmol) at −44° C. under argon, the reaction was slowly warmed to room temperature, and stirred for 10 min. Saturated NH4Cl was added, the resulting mixture was extracted several times with EtOAc, the combined organic layer dried, filtered through a silica gel pad, and concentrated to give yellow oil. The oil was dissolved in CH2Cl2 (2 ml), then pyridine (80 μl, 0.9 mmol) and ethyl chloroformate (50 μμl, 0.5 mmol) were added, the mixture was stirred at room temperature for 30 min, stirred for another 10 min after which H2O (25 μl) and EtOAc were added, and the mixture dried over Na2SO4, filtered through a silica gel pad, and concentrated to give yellow oil. The oil was dissolved in CH3CN (2 ml), H2O (0.3 ml) and TFA (0.2 ml) were added, and the mixture stirred at room temperature for 2 h. Saturated NaHCO3 solution and EtOAc were added, the aqueous layer was separated and extracted with EtOAc, and the combined organic layer was dried over Na2SO4, concentrated and chromatographed on silica gel to give 35 mg of desired product as yellow foam (60%). MS (M+H)+=392. HPLC RT=3.60 min (YMC S5 ODS column 4.6×50 mm, 10-90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 ml/min, monitoring at 220 nm).

Workup

  1. extractionthe resulting mixture was extracted several times with EtOAc
  2. customthe combined organic layer dried
  3. filtrationfiltered through a silica gel pad
  4. concentrationconcentrated
  5. customto give yellow oil
  6. stirringthe mixture was stirred at room temperature for 30 min
  7. additionwere added
  8. dry with materialthe mixture dried over Na2SO4
  9. filtrationfiltered through a silica gel pad
  10. concentrationconcentrated
  11. customto give yellow oil
  12. stirringthe mixture stirred at room temperature for 2 h
  13. customthe aqueous layer was separated
  14. extractionextracted with EtOAc
  15. dry with materialthe combined organic layer was dried over Na2SO4
  16. concentrationconcentrated
  17. customchromatographed on silica gel

Sources & evidence

ORD record
ord-04dc0666327746b19bad33d3bd8b3b97
Source dataset
uspto-grants-2005_05
Patent number
US06900214B2

Reaction notes

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