Citric Acid → HCID 86641356, compound

HRID 1693330Notes

Reaction equation

HRID 1693330 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[C:10]2[C:11]3[C:12](=[N:22][N:23]([CH2:25][C:26]4[C:31]([CH3:32])=[C:30]([O:33][CH3:34])[C:29]([CH3:35])=[CH:28][N:27]=4)[N:24]=2)[CH:13]=[C:14]([C:19](O)=[O:20])[C:15]=3[CH2:16][S:17][N:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC)=O.[BH4-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.CO>[OH:20][CH2:19][C:14]1[C:15]2[CH2:16][S:17][N:18]=[C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[C:10]3=[N:24][N:23]([CH2:25][C:26]4[C:31]([CH3:32])=[C:30]([O:33][CH3:34])[C:29]([CH3:35])=[CH:28][N:27]=4)[N:22]=[C:12]([C:11]=23)[CH:13]=1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 67280154HCID 67280154, compound

Product 1

HCID 86641356HCID 86641356, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-[(tert-Butoxycarbonyl)amino]-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-2,7-dihydro-6-thia-1,2,3,5-tetraazabenzo[cd]azulen-8-carboxylic acid (50 mg) was dissolved in tetrahydrofuran (1 ml) under cooling in an ice bath. N-Methylmorpholine (13 μl) and ethyl chloroformate (12 μl) were added, followed by stirring for two hours. Subsequently, sodium borohydride (12 mg) and methanol (1 ml) were added to the reaction solution, and the mixture was stirred for three hours while gradually returning to room temperature. A 10% citric acid solution was added to the reaction solution, followed by extraction with ethyl acetate. The resulting organic layer was sequentially washed with a saturated sodium bicarbonate solution and brine and dried over anhydrous sodium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (chloroform-methanol) to obtain the title compound as an oil (35 mg, 72%).

Workup

  1. temperatureunder cooling in an ice bath
  2. stirringthe mixture was stirred for three hours
  3. customwhile gradually returning to room temperature
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe resulting organic layer was sequentially washed with a saturated sodium bicarbonate solution and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customthe resulting residue was purified by silica gel column chromatography (chloroform-methanol)

Sources & evidence

ORD record
ord-b11c98d88e9149878d681ef78f6730ff
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

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