Hydrochloric Acid → HCID 67040443, compound

HRID 605198Notes

Reaction equation

HRID 605198 reaction equation
C1C2C(COC(=O)[NH:17][C:18]3[CH:23]=[CH:22][C:21]([S:24][C:25]4[CH:30]=[CH:29][C:28]([C:31](=[O:39])[NH:32][C:33]5[S:37][N:36]=[C:35]([CH3:38])[CH:34]=5)=[CH:27][C:26]=4[NH:40][C:41]4[C:42]5[CH:50]=[CH:49][C:48]([CH:51]([CH3:53])[CH3:52])=[N:47][C:43]=5[N:44]=[CH:45][N:46]=4)=[CH:20][CH:19]=3)C3C(=CC=CC=3)C=2C=CC=1.O.[OH-].[Li+].Cl>O1CCOCC1.O.C(OCC)(=O)C>[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([S:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([NH:32][C:33]3[S:37][N:36]=[C:35]([CH3:38])[CH:34]=3)=[O:39])=[CH:27][C:26]=2[NH:40][C:41]2[C:42]3[CH:50]=[CH:49][C:48]([CH:51]([CH3:53])[CH3:52])=[N:47][C:43]=3[N:44]=[CH:45][N:46]=2)=[CH:20][CH:19]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 67040295HCID 67040295, compound

Product 1

HCID 67040443HCID 67040443, compoundYield 71.1%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
70 °C

Procedure

A solution of the product of Example 167C (117 mg, 0.156 mmol) in 1,4-dioxane (4 mL) was treated with a solution of lithium hydroxide monohydrate (13.1 mg, 0.312 mmol) in water (2 mL) at ambient temperature, then heated at 70° C. for 1 hour. The reaction was cooled to room temperature, diluted with ethyl acetate (50 mL) and water (25 mL), adjusted the aqueous pH to 5 with 1N aqueous hydrochloric acid, and separated the layers. The organic phase was washed with water (2×25 mL) and brine (25 mL), dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation in vacuo. Purification of the residue by silica gel chromatography eluting with 5% methanol/methylene chloride afforded the title compound as a light yellow solid (58.5 mg, 71%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.34 (d, J=6.99 Hz, 6 H) 2.33 (s, 3 H) 3.14-3.30 (m, 1 H) 5.63 (s, 2 H) 6.65 (d, J=8.46 Hz, 2 H) 6.87 (s, 1 H) 6.91 (d, J=8.82 Hz, 1 H) 7.15 (d, J=8.46 Hz, 2 H) 7.65 (d, J=8.09 Hz, 1 H) 7.86 (d, J=7.72 Hz, 1 H) 8.03 (s, 1 H) 8.59 (s, 1 H) 8.89 (d, J=8.09 Hz, 1 H) 10.19 (s, 1 H) 12.17 (s, 1 H); MS (ESI+) m/z 528 (M+H)+, (ESI−) m/z 526 (M−H)−.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customseparated the layers
  3. washThe organic phase was washed with water (2×25 mL) and brine (25 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation in vacuo
  7. customPurification of the residue by silica gel chromatography
  8. washeluting with 5% methanol/methylene chloride

Sources & evidence

ORD record
ord-c5fe3db93ee0498a9da20f21cdb0e2cc
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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