Citric Acid → 6-[4-Methoxy-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]-N-(methylsulfonyl)pyridine-2-carboxamide

HRID 873520Notes

Reaction equation

HRID 873520 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[N:26]=[C:25]([C:27]([OH:29])=O)[CH:24]=[CH:23][CH:22]=2)=[CH:17][C:16]=1[CH:30]1[C:43]2[C:42](=[O:44])[CH2:41][C:40]([CH3:46])([CH3:45])[CH2:39][C:38]=2[O:37][C:36]2[CH2:35][C:34]([CH3:48])([CH3:47])[CH2:33][C:32](=[O:49])[C:31]1=2.[CH3:50][S:51]([NH2:54])(=[O:53])=[O:52].N12CCCN=C1CCCCC2.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[N:26]=[C:25]([C:27]([NH:54][S:51]([CH3:50])(=[O:53])=[O:52])=[O:29])[CH:24]=[CH:23][CH:22]=2)=[CH:17][C:16]=1[CH:30]1[C:43]2[C:42](=[O:44])[CH2:41][C:40]([CH3:46])([CH3:45])[CH2:39][C:38]=2[O:37][C:36]2[CH2:35][C:34]([CH3:47])([CH3:48])[CH2:33][C:32](=[O:49])[C:31]1=2

Participants

7

Reactant 5

HCID 311Citric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 117700629HCID 117700629, compound

Product 1

HCID 1177007736-[4-Methoxy-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]-N-(methylsulfonyl)pyridine-2-carboxamideYield 56.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1,1′-Carbonyldiimidazole (54.6 mg, 0.34 mmol) was added to a solution of the 6-[4-methoxy-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyridine-2-carboxylic acid produced in Example 1-2 (130 mg, 0.26 mmol) in DMF (2.6 ml) at room temperature, and the mixture thus obtained was then stirred at the same temperature as above for 2 hours. Thereafter, methanesulfonamide (32.1 mg, 0.34 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.050 ml, 0.34 mmol) were added to the resulting solution at room temperature, and the mixture thus obtained was then stirred at the same temperature as above for 71 hours. Thereafter, an aqueous solution of citric acid (249 mg, 1.30 mmol) was added to the reaction solution, and the mixed solution was then extracted with ethyl acetate. The organic layer thus obtained was washed with water, and was then dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the residue thus obtained was then purified by silica gel column chromatography (methanol:dichloromethane=0:1 to 1:9, v/v). Ethanol was added to the fraction thus obtained, and the generated solid was then collected by filtration and dried to obtain the title compound (84.4 mg, yield: 56%).

Workup

  1. customthe mixture thus obtained
  2. customthe mixture thus obtained
  3. stirringwas then stirred at the same temperature as above for 71 hours
  4. extractionthe mixed solution was then extracted with ethyl acetate
  5. customThe organic layer thus obtained
  6. washwas washed with water
  7. dry with materialwas then dried over anhydrous sodium sulfate
  8. distillationThe solvent was distilled away under reduced pressure
  9. customthe residue thus obtained
  10. customwas then purified by silica gel column chromatography (methanol:dichloromethane=0:1 to 1:9, v/v)
  11. additionEthanol was added to the fraction
  12. customthus obtained
  13. filtrationthe generated solid was then collected by filtration
  14. customdried

Sources & evidence

ORD record
ord-529a36da23d640678af2aa6296fcd9b6
Source dataset
uspto-grants-2015_03
Patent number
US08975263B2

Reaction notes

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