Hydrochloric Acid → HCID 73855138, compound

HRID 2121977Notes

Reaction equation

HRID 2121977 reaction equation
[CH2:1]([N:8]1[C:12](=[O:13])[C:11](=[C:14]2[N:18]([CH3:19])[C:17]3[CH:20]=[C:21]([O:24][CH2:25][CH2:26]Cl)[CH:22]=[CH:23][C:16]=3[S:15]2)[S:10][C:9]1=[N:28][C:29]1[CH:30]=[C:31]([NH:38][C:39](=[O:44])[CH2:40][N:41]([CH3:43])[CH3:42])[CH:32]=[CH:33][C:34]=1[NH:35][CH2:36][CH3:37])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=[O:47])C.[Na+].[OH-].[Na+].Cl>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O.CO.CN(C=O)C>[CH2:1]([N:8]1[C:12](=[O:13])[C:11](=[C:14]2[N:18]([CH3:19])[C:17]3[CH:20]=[C:21]([O:24][CH2:25][CH2:26][OH:47])[CH:22]=[CH:23][C:16]=3[S:15]2)[S:10][C:9]1=[N:28][C:29]1[CH:30]=[C:31]([NH:38][C:39](=[O:44])[CH2:40][N:41]([CH3:43])[CH3:42])[CH:32]=[CH:33][C:34]=1[NH:35][CH2:36][CH3:37])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 517045Sodium AcetateHCID 73854978HCID 73854978, compound

Product 1

HCID 73855138HCID 73855138, compoundYield 5.3%

Reagents, catalysts & solvents 4

HCID 67553Tetrabutylammonium IodideCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

To an 8 mL vial was added the product of Example 145 (100 mg, 0.15 mmol), anhydrous DMF (5 mL), and tetra-n-butylammonium iodide (570 mg, 1.54 mmol). The solution was heated at 75° C. for 4 h prior to the addition of sodium acetate (250 mg, 3.08 mmol). The reaction solution was then heated 16 h at 75° C. To the solution was added MeOH (2 mL), 5M aqueous NaOH (1 mL) and H2O (1 mL). After heating at 50° C. for 5 h, the reaction mixture was cooled, neutralized with conc HCl and concentrated under reduced pressure. The residue was taken up into DCM (50 mL), and the organic phase was washed with water (2×25 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was chromatographed (SiO2, 0-10% MeOH/DCM) to provide the title compound (5 mg, 5%). 1H NMR (MeOH-d4): δ 8.92 (1H, s), 7.11-7.26 (7H, m), 6.97 (1H, dd), 6.66 (1H, dd), 6.60 (1H, d), 6.44 (1H, d), 5.01 (2H, s), 3.96 (2H, t), 3.77 (2H, t), 3.62 (3H, s), 3.00 (2H, s), 2.82 (2H, q), 2.28 (6H, s), 0.89 (3H, t); MS(ESI) 633 (MH+).

Workup

  1. temperatureThe reaction solution was then heated 16 h at 75° C
  2. temperatureAfter heating at 50° C. for 5 h
  3. temperaturethe reaction mixture was cooled
  4. concentrationconcentrated under reduced pressure
  5. washthe organic phase was washed with water (2×25 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was chromatographed (SiO2, 0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-900a94727ec54828925c355765fe2e4e
Source dataset
uspto-grants-2004_02
Patent number
US06696473B2

Reaction notes

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