creatinine → HCID 178439308, compound

HRID 1735848Notes

Reaction equation

HRID 1735848 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][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:12])=[O:11])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[NH2:39][C:40]1[N:41]([CH3:46])[CH2:42][C:43](=[O:45])[N:44]=1.C(N(CC)CC)C>C1COCC1>[CH3:46][N:41]1[CH2:42][C:43](=[O:45])[N:44]=[C:40]1[NH:39][C:23]([C:20]1[CH:21]=[CH:22][C:17]([O:16][CH:15]([C:29]2[CH:34]=[CH:33][C:32]3[O:35][CH2:36][O:37][C:31]=3[CH:30]=2)[C:14]([NH:13][S:10]([C:7]2[CH:6]=[CH:5][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:9][CH:8]=2)(=[O:11])=[O:12])=[O:38])=[C:18]([CH2:26][CH2:27][CH3:28])[CH:19]=1)=[O:24]

Participants

5

Reactant 3

HCID 588creatinineHCID 8471TriethylamineHCID 98944604-[1-(1,3-Benzodioxol-5-yl)-2-oxo-2-[(4-propan-2-ylphenyl)sulfonylamino]ethoxy]-3-propylbenzoic acid

Product 1

HCID 178439308HCID 178439308, compoundYield 60.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 200 mg (0.370 mmol) of N-(4-isopropylbenzenesulfonyl)-α-(4-carboxy-2-n-propylphenoxy)-3,4-methylenedioxyphenylacetamide (from Step D) in 1 mL of dry THF was added 90 mg (0.556 mmol) of 1,1-carbonyldiimidazole. The solution was stirred at reflux under N2 for 2 hours. The cooled solution was evaporated to dryness. The residue was dissolved in 1 mL of acetonitrile and treated with 63 mg (0.556 mmol) of 2-amino-4,5-dihydro-1-methyl-1H-imidazol-4-one (creatinine) and 129 μL (93.7 mg; 0.925 mmol) of triethylamine. The mixture was stirred at reflux overnight. The cooled reaction mixture was quenched by addition of 1N HCl and extracted twice with EtOAc. The combined organic extracts were dried over MgSO4, and filtered. The filtrate was concentrated, and the residue was flash chromatographed (silica gel, 27×3.5 cm; elution with 500 mL of 99:1:1 CHCl3 -MeOH-concentrated NH4OH followed by 1 L of 85:15:1 CHCl3 -MeOH-concentrated NH4OH) to give 142 mg (60%) of the title compound as a yellow solid, mp 137°-139 ° C.; homogeneous by TLC in 85:15:1 CHCl3 -MeOH-concentrated NH4OH. ESI mass spectrum m/e 635 (M+H)+.

Workup

  1. temperatureat reflux under N2 for 2 hours
  2. customThe cooled solution was evaporated to dryness
  3. dissolutionThe residue was dissolved in 1 mL of acetonitrile
  4. stirringThe mixture was stirred
  5. temperatureat reflux overnight
  6. customThe cooled reaction mixture
  7. customwas quenched by addition of 1N HCl
  8. extractionextracted twice with EtOAc
  9. dry with materialThe combined organic extracts were dried over MgSO4
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated
  12. customchromatographed
  13. wash(silica gel, 27×3.5 cm; elution with 500 mL of 99:1:1 CHCl3 -MeOH-concentrated NH4OH followed by 1 L of 85:15:1 CHCl3 -MeOH-concentrated NH4OH)

Sources & evidence

ORD record
ord-c069f92d4b554fed81e4a56794fc691a
Source dataset
uspto-grants-1996_07
Patent number
US05538991

Reaction notes

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