Hydrochloric Acid → HCID 67040280, compound

HRID 605232Notes

Reaction equation

HRID 605232 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:40])[NH:32][C:33]5[CH:34]=[N:35][CH:36]=[C:37]([F:39])[CH:38]=5)=[CH:27][C:26]=4[NH:41][C:42]4[C:43]5[CH:51]=[CH:50][C:49]([CH:52]([CH3:54])[CH3:53])=[N:48][C:44]=5[N:45]=[CH:46][N:47]=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[CH:34]=[N:35][CH:36]=[C:37]([F:39])[CH:38]=3)=[O:40])=[CH:27][C:26]=2[NH:41][C:42]2[C:43]3[CH:51]=[CH:50][C:49]([CH:52]([CH3:54])[CH3:53])=[N:48][C:44]=3[N:45]=[CH:46][N:47]=2)=[CH:20][CH:19]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 67040577HCID 67040577, compound

Product 1

HCID 67040280HCID 67040280, compoundYield 61%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
70 °C

Procedure

A solution of the product of Example 224F (118.9 mg, 0.159 mmol) in 1,4-dioxane (3 mL) was treated with a solution of lithium hydroxide monohydrate (13.3 mg, 0.318 mmol) in water (1.5 mL) at ambient temperature, then heated at 70° C. for 45 minutes. The reaction was cooled to room temperature, diluted with ethyl acetate (100 mL) and water (30 mL), adjusted the aqueous pH to 6 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 yellow solid (51 mg, 61%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.34 (d, J=6.99 Hz, 6 H) 3.10-3.34 (m, 1 H) 5.61 (s, 2 H) 6.64 (d, J=8.46 Hz, 2 H) 6.90 (d, J=8.09 Hz, 1 H) 7.15 (d, J=8.46 Hz, 2 H) 7.65 (d, J=8.09 Hz, 1 H) 7.81 (dd, J=7.17, 1.65 Hz, 1 H) 7.97 (s, 1 H) 8.13-8.23 (m, 1 H) 8.32 (d, J=2.57 Hz, 1 H) 8.59 (s, 1 H) 8.76 (d, J=1.47 Hz, 1 H) 8.89 (d, J=8.09 Hz, 1 H) 10.18 (s, 1 H) 10.59 (s, 1 H); MS (ESI+) m/z 526 (M+H)+, (ESI−) m/z 524 (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-3174b8e2244c4f909115d03cb5ac3b26
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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