Water → HCID 86731228, compound

HRID 2277172Notes

Reaction equation

HRID 2277172 reaction equation
Cl[C:2]1[C:7]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH:18]3[CH2:20][CH2:19]3)=[C:12]([Cl:21])[CH:11]=2)=[CH:6][N:5]=[C:4]([O:23][CH2:24][C@@H:25]([NH:27][C:28](=[O:34])OC(C)(C)C)[CH3:26])[CH:3]=1.[C:35](=O)([O-])[O-].[K+].[K+].O>CN(C=O)C.[Cu]I>[Cl:21][C:12]1[CH:11]=[C:10]([C:9]2[O:22][C:2]3[CH:3]=[C:4]([O:23][CH2:24][C@@H:25]([NH:27][C:28](=[O:34])[CH3:35])[CH3:26])[N:5]=[CH:6][C:7]=3[N:8]=2)[CH:15]=[CH:14][C:13]=1[O:16][CH2:17][CH:18]1[CH2:19][CH2:20]1

Participants

6

Reactant 3

HCID 962WaterHCID 11430Potassium CarbonateHCID 86731229HCID 86731229, compound

Product 1

HCID 86731228HCID 86731228, compoundYield 11.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

A suspension of tert-butyl ((2S)-1-((4-chloro-5-((3-chloro-4-(cyclopropylmethoxy)benzoyl)amino)pyridin-2-yl)oxy)propan-2-yl)carbamate (1.02 g), potassium carbonate (0.552 g) and copper(I) iodide (38.0 mg) in DMF (10 mL) was stirred at 160° C. for 5 hr under microwave irradiation. To the reaction mixture was added water, and the obtained mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and subjected to silica gel column chromatography (NH, ethyl acetate). The solvent was evaporated, and to the obtained residue was added 2 M hydrogen chloride/methanol (5 mL), and the mixture was stirred at room temperature for 10 min, and concentrated. To the residue were added pyridine (5 mL) and acetic anhydride (5 mL), and the mixture was stirred at room temperature for 15 min. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate) to give the title compound (92.4 mg). 1H NMR (300 MHz, CDCl3) δ 0.38-0.48 (2H, m), 0.64-0.77 (2H, m), 1.30 (3H, d, J=6.4 Hz), 1.33-1.44 (1H, m), 1.97 (3H, s), 3.99 (2H, d, J=6.8 Hz), 4.25-4.51 (3H, m), 6.01 (1H, d, J=6.0 Hz), 6.91 (1H, s), 7.02 (1H, d, J=8.7 Hz), 8.06 (1H, dd, J=8.7, 1.9 Hz), 8.24 (1H, d, J=2.3 Hz), 8.53 (1H, s).

Workup

  1. extractionthe obtained mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. customThe solvent was evaporated
  4. additionto the obtained residue was added 2 M hydrogen chloride/methanol (5 mL)
  5. stirringthe mixture was stirred at room temperature for 10 min
  6. concentrationconcentrated
  7. additionTo the residue were added pyridine (5 mL) and acetic anhydride (5 mL)
  8. stirringthe mixture was stirred at room temperature for 15 min
  9. concentrationThe reaction mixture was concentrated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate)

Sources & evidence

ORD record
ord-9baf3c6442934c6498c29a8700d3ce55
Source dataset
uspto-grants-2015_09
Patent number
US09133129B2

Reaction notes

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