Tetrahydrofuran → HCID 22912475, compound

HRID 1378874Notes

Reaction equation

HRID 1378874 reaction equation
C(C1C=CC(S(N[C:14](=[O:38])[CH:15]([C:29]2[CH:34]=[CH:33][C:32]3[O:35][CH2:36][O:37][C:31]=3[CH:30]=2)[O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23](O)=[O:24])=[CH:19][C:18]=2[CH2:26][CH2:27][CH3:28])(=O)=O)=CC=1)(C)C.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:51][S:52]([NH2:55])(=[O:54])=[O:53].[CH2:56]1[CH2:66][CH2:65]N2C(=NCCC2)[CH2:58][CH2:57]1.O1C[CH2:70][CH2:69][CH2:68]1>>[CH:69]([C:56]1[CH:57]=[CH:58][C:51]([S:52]([NH:55][C:14](=[O:38])[CH:15]([C:29]2[CH:34]=[CH:33][C:32]3[O:35][CH2:36][O:37][C:31]=3[CH:30]=2)[O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23](=[O:24])[NH:55][S:52]([CH3:51])(=[O:54])=[O:53])=[CH:19][C:18]=2[CH2:26][CH2:27][CH3:28])(=[O:54])=[O:53])=[CH:65][CH:66]=1)([CH3:70])[CH3:68]

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 98944604-[1-(1,3-Benzodioxol-5-yl)-2-oxo-2-[(4-propan-2-ylphenyl)sulfonylamino]ethoxy]-3-propylbenzoic acid

Product 1

HCID 22912475HCID 22912475, compoundYield 96%

Procedure

A solution of 146 mg (0.271 mmol) of N-(4-iso-propylbenzenesulfonyl)-α-(4-carboxy-2-n-propylphenoxy)-3,4-methylenedioxyphenylacetamide (free acid form of the product of Example 58) and 66 mg (0.406 mmol) of 1,1'-carbonyldiimidazole in 1 mL of dry tetrahydrofuran was refluxed for 1.5 hours. The reaction mixture was cooled to room temperature and 39 mg (0.406 mmol) of methanesulfonamide and 101 μL (0.667 mmol) of DBU were added and the mixture was refluxed again. The reaction progress was monitored by analytical HPLC analysis using a Waters 600E HPLC system with a 4.6×250 mm 5 μM Zorbax C18 column at 40° C. and eluting isocratically 1.5 mL/min using 60% A (95-5 acetonitrile-water) 40% B (95-5 water-acetonitrile) each with 0.1% TFA where the column effluent was monitored simultaneously at 210 and 277 nM with a Waters model 490 UV-visible detector. After 1.0 hour of additional refluxing, analytical HPLC analysis indicated that the coupling was complete. The reaction mixture poured into 1N HCl and extracted with ethyl acetate, washed with brine, dried over magnesium surf ate, filtered, and the filtrate evaporated in vacuo to afford 160 mg (96%) of the title compound as an amorphous solid.

Workup

  1. temperaturethe mixture was refluxed again
  2. customat 40° C.
  3. washeluting isocratically 1.5 mL/min
  4. additionThe reaction mixture poured into 1N HCl
  5. extractionextracted with ethyl acetate
  6. washwashed with brine
  7. dry with materialdried over magnesium
  8. filtrationfiltered
  9. customthe filtrate evaporated in vacuo

Sources & evidence

ORD record
ord-eef9534518d84ca9aac02eb3b858020f
Source dataset
uspto-grants-1997_09
Patent number
US05668176

Reaction notes

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