Tetrahydrofuran → HCID 86641346, compound

HRID 1693313Notes

Reaction equation

HRID 1693313 reaction equation
[BH4-].[Li+].[C:3]([O:7][C:8]([N:10](C(OC(C)(C)C)=O)[C:11]1[C:12]2[C:13]3[C:14](=[N:26][N:27]([CH2:29][C:30]4[C:35]([CH3:36])=[C:34]([O:37][CH3:38])[C:33]([CH3:39])=[CH:32][N:31]=4)[N:28]=2)[CH:15]=[C:16]([CH2:21][C:22](OC)=[O:23])[C:17]=3[CH2:18][S:19][N:20]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].O1CCCC1.[OH-].[Na+]>CO>[OH:23][CH2:22][CH2:21][C:16]1[C:17]2[CH2:18][S:19][N:20]=[C:11]([NH:10][C:8](=[O:9])[O:7][C:3]([CH3:4])([CH3:5])[CH3:6])[C:12]3=[N:28][N:27]([CH2:29][C:30]4[C:35]([CH3:36])=[C:34]([O:37][CH3:38])[C:33]([CH3:39])=[CH:32][N:31]=4)[N:26]=[C:14]([C:13]=23)[CH:15]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 4148881Lithium borohydride2×HCID 86641343HCID 86641343, compound

Product 1

HCID 86641346HCID 86641346, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Lithium borohydride (67 mg) was added to a mixture composed of methyl {4-[bis(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-yl}acetate of Example 111 (957 mg) and dehydrated tetrahydrofuran (18 ml) under ice-cooling. The mixture was stirred at 0° C. for two hours, and then returned to room temperature and stirred overnight. The mixture was ice-cooled again and lithium borohydride (33 mg) was added, followed by stirring at 0° C. for two hours. Methanol (6 ml) and a 1 N sodium hydroxide solution (6 ml) were added to the reaction mixture. Then, the mixture was returned to room temperature and stirred for four hours. The organic solvent in the reaction mixture was evaporated under reduced pressure. Then, a 0.2 N hydrochloric acid solution was added, followed by extraction with chloroform. The organic layer was washed with brine, and then dried over magnesium sulfate and filtered. Then, the filtrate was concentrated under reduced pressure. The concentrated residue was purified by silica gel column chromatography (chloroform-methanol) to obtain the title compound (301 mg, 40%) as an oil.

Workup

  1. temperaturecooling
  2. customreturned to room temperature
  3. stirringstirred overnight
  4. temperaturecooled again
  5. stirringby stirring at 0° C. for two hours
  6. customwas returned to room temperature
  7. stirringstirred for four hours
  8. customThe organic solvent in the reaction mixture was evaporated under reduced pressure
  9. additionThen, a 0.2 N hydrochloric acid solution was added
  10. extractionfollowed by extraction with chloroform
  11. washThe organic layer was washed with brine
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationThen, the filtrate was concentrated under reduced pressure
  15. customThe concentrated residue was purified by silica gel column chromatography (chloroform-methanol)

Sources & evidence

ORD record
ord-52de5930f58d4a899cba73f47820729d
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

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