Methanol → HCID 178480292, compound

HRID 536748Notes

Reaction equation

HRID 536748 reaction equation
[CH3:1][C:2]([CH3:5])([O-:4])[CH3:3].[K+].[C:7]([C:11]1[N:15]([CH3:16])[N:14]([CH2:17][CH:18]2[CH2:21][CH2:20][CH2:19]2)/[C:13](=[N:22]/[C:23](=[O:33])[C:24]2[CH:29]=[C:28]([C:30]#[N:31])[CH:27]=[CH:26][C:25]=2F)/[CH:12]=1)([CH3:10])([CH3:9])[CH3:8].CC[O:36]C(C)=O.CO>C1COCC1.CCN(CC)CC>[C:7]([C:11]1[N:15]([CH3:16])[N:14]([CH2:17][CH:18]2[CH2:21][CH2:20][CH2:19]2)/[C:13](=[N:22]/[C:23](=[O:33])[C:24]2[CH:29]=[C:28]([C:30]#[N:31])[CH:27]=[CH:26][C:25]=2[O:36][CH2:1][C:2]([OH:4])([CH3:5])[CH3:3])/[CH:12]=1)([CH3:10])([CH3:9])[CH3:8]

Participants

7

Reactant 4

HCID 887MethanolHCID 8857Ethyl Acetate2×HCID 23665647Potassium tert-butoxideHCID 178480291HCID 178480291, compound

Product 1

HCID 178480292HCID 178480292, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of Example 81D (0.26 g, 2.9 mmol) in THF (10 mL) at ambient temperature was added potassium tert-butoxide (0.55 g, 4.9 mmol). The mixture was allowed to stir for 20 minutes at ambient temperature then a solution of Example 113D (0.60 g, 1.6 mmol) in THF (5 mL) was added via cannula. The mixture was stirred at ambient temperature for 3 hours then the mixture was quenched with saturated aqueous NaHCO3 (5 mL) and was diluted with EtOAc (10 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×5 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, concentrated and purified via column chromatography (SiO2, 50% hexanes/EtOAc then 100% EtOAc then 9:1:0.1 EtOAc:MeOH:Et3N) to afford the title compound (0.43 g, 0.98 mmol, 60% yield). 1H NMR (300 MHz, CDCl3) δ ppm 1.29 (s, 6H) 1.41 (s, 9H) 1.80-1.92 (m, 4H) 1.98-2.07 (m, 2H) 2.53-2.73 (m, 1H) 3.73 (s, 3H) 4.03 (s, 2H) 4.33 (d, J=7.1 Hz, 2H) 6.04 (s, 1H) 6.99 (d, J=8.3 Hz, 1H) 6.99 (s, 1H) 7.56 (dd, J=8.5, 2.2 Hz, 1H) 8.15 (d, J=2.0 Hz, 1H); MS (ESI+) m/z 439 (M+H)+; Anal. calculated for C25H34N4O3: Calc: C, 68.47; H, 7.81; N, 12.78. Found: C, 68.27; H, 7.47; N, 12.68.

Workup

  1. stirringThe mixture was stirred at ambient temperature for 3 hours
  2. customthe mixture was quenched with saturated aqueous NaHCO3 (5 mL)
  3. additionwas diluted with EtOAc (10 mL)
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with EtOAc (3×5 mL)
  6. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified via column chromatography (SiO2, 50% hexanes/EtOAc

Sources & evidence

ORD record
ord-39ff0a5fde3943e6a5e096c5b1285718
Source dataset
uspto-grants-2014_10
Patent number
US08859596B2

Reaction notes

Loading…