Hydrochloric Acid → HCID 67040493, compound

HRID 605186Notes

Reaction equation

HRID 605186 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](=[O:27])[NH:21][CH:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)=[CH:16][C:15]=2[NH:28][C:29]2[C:30]3[CH:38]=[CH:37][C:36]([CH:39]([CH3:41])[CH3:40])=[N:35][C:31]=3[N:32]=[CH:33][N:34]=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]([NH:21][CH:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)=[O:27])=[CH:16][C:15]=2[NH:28][C:29]2[C:30]3[CH:38]=[CH:37][C:36]([CH:39]([CH3:41])[CH3:40])=[N:35][C:31]=3[N:32]=[CH:33][N:34]=2)=[CH:9][CH:8]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67040551HCID 67040551, compound

Product 1

HCID 67040493HCID 67040493, compoundYield 64.4%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
60 °C

Procedure

A solution of the product of Example 155A (39.9 mg, 0.0592 mmol) in 1,4-dioxane (2 mL) was treated with a solution of sodium hydroxide (5.9 mg, 0.148 mmol) in water (1 mL), then heated at 60° C. for 1 hour. 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 4% methanol/methylene chloride provided the title compound as a white solid (19 mg, 64%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.34 (d, J=6.62 Hz, 6 H) 1.43-1.58 (m, 4 H) 1.59-1.75 (m, 2 H) 1.78-1.96 (m, 2 H) 3.12-3.32 (m, 1 H) 4.11-4.26 (m, 1 H) 5.57 (s, 2 H) 6.61 (d, J=8.46 Hz, 2 H), 6.81 (d, J=8.82 Hz, 1 H) 7.11 (d, J=8.46 Hz, 2 H) 7.64 (t, J=9.01 Hz, 1 H) 7.83 (s, 1 H) 8.21 (d, J=6.62 Hz, 1 H) 8.56 (s, 1 H) 8.86 (d, J=8.82 Hz, 1 H) 10.10 (s, 1 H); MS (ESI+) m/z 499 (M+)+, (ESI−) m/z 497 (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 4% methanol/methylene chloride

Sources & evidence

ORD record
ord-b29ffe588e054c1ba7507964227d11a6
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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