Hydrochloric Acid → HCID 25117304, compound

HRID 605208Notes

Reaction equation

HRID 605208 reaction equation
ClC(Cl)(Cl)COC(=O)[NH:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]([N:22]3[CH2:27][CH:26]([CH3:28])[O:25][CH:24]([CH3:29])[CH2:23]3)=[O:21])=[CH:16][C:15]=2[NH:30][C:31]2[C:32]3[CH:40]=[CH:39][C:38]([CH:41]([CH3:43])[CH3:42])=[N:37][C:33]=3[N:34]=[CH:35][N:36]=2)=[CH:9][CH:8]=1.[OH-].[Na+].Cl>O1CCOCC1.O.C(OCC)(=O)C>[NH2:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]([N:22]3[CH2:27][CH:26]([CH3:28])[O:25][CH:24]([CH3:29])[CH2:23]3)=[O:21])=[CH:16][C:15]=2[NH:30][C:31]2[C:32]3[CH:40]=[CH:39][C:38]([CH:41]([CH3:43])[CH3:42])=[N:37][C:33]=3[N:34]=[CH:35][N:36]=2)=[CH:9][CH:8]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67040718HCID 67040718, compound

Product 1

HCID 25117304HCID 25117304, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of the product of Example 179A (56 mg, 0.0795 mmol) in 1,4-dioxane (2 mL) was treated with a solution of sodium hydroxide (8 mg, 0.1988 mmol) in water (1 mL), and heated at 60° C. for 30 minutes. The reaction was then cooled to room temperature and diluted with ethyl acetate (50 mL) and water (25 mL). The aqueous pH was adjusted to 5 with 1N aqueous hydrochloric acid, the layers were separated, and the organic phase washed with water (2×25 mL) and brine (25 mL). The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation in vacuo. Purification of the residue by silica gel flash chromatography with 5% methanol/methylene chloride provided the title compound as an off-white solid (18 mg, 43%). 1H NMR (300 MHz, DMSO-d6/TFA) δ ppm: 0.91-1.25 (m, 6 H) 1.37 (d, J=6.99 Hz, 6 H) 2.70-2.97 (m, 1 H) 3.25-3.40 (m, 1 H) 3.45-3.64 (m, 4 H) 4.20-4.52 (m, 1 H) 5.72 (s, 2 H) 7.29 (d, J=8.09 Hz, 1 H) 7.35 (d, J=8.46 Hz, 2 H) 7.48 (dd, J=7.91, 2.02 Hz, 1 H) 7.50 (d, J=8.45 Hz, 2 H) 7.60 (d, J=1.84 Hz, 1 H) 7.96 (d, J=8.82 Hz, 1 H) 8.97 (s, 1 H) 9.07 (d, J=8.82 Hz, 1 H); MS (ESI+) m/z 529 (M+H)+, (ESI−) m/z 527 (M−H)−.

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. customthe layers were separated
  3. washthe organic phase washed with water (2×25 mL) and brine (25 mL)
  4. extractionThe organic extract
  5. dry with materialwas dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation in vacuo
  8. customPurification of the residue by silica gel flash chromatography with 5% methanol/methylene chloride

Sources & evidence

ORD record
ord-a8028ae39af54d67afa6f54b8fe7f8c4
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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