4-Methylmorpholine → HCID 86641344, compound

HRID 1693306Notes

Reaction equation

HRID 1693306 reaction equation
CN1CCOCC1.[C:8]([O:12][C:13]([N:15]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:16]1[C:17]2[C:18]3[C:19](=[N:30][N:31]([CH2:33][C:34]4[C:39]([CH3:40])=[C:38]([O:41][CH3:42])[C:37]([CH3:43])=[CH:36][N:35]=4)[N:32]=2)[CH:20]=[C:21]([CH2:26][C:27](O)=[O:28])[C:22]=3[CH2:23][S:24][N:25]=1)=[O:14])([CH3:11])([CH3:10])[CH3:9].O1CCCC1.ClC(OCC(C)C)=O>O>[OH:28][CH2:27][CH2:26][C:21]1[C:22]2[CH2:23][S:24][N:25]=[C:16]([N:15]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:13]([O:12][C:8]([CH3:11])([CH3:9])[CH3:10])=[O:14])[C:17]3=[N:32][N:31]([CH2:33][C:34]4[C:39]([CH3:40])=[C:38]([O:41][CH3:42])[C:37]([CH3:43])=[CH:36][N:35]=4)[N:30]=[C:19]([C:18]=23)[CH:20]=1

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 8028TetrahydrofuranHCID 62365Isobutyl chloroformate2×HCID 67280836HCID 67280836, compound

Product 1

HCID 86641344HCID 86641344, compoundYield 27.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

N-Methylmorpholine (22 μl) was added to a mixture composed of the above {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}acetic acid (60 mg) and tetrahydrofuran (2 ml). Then, isobutyl chloroformate (39 μl) was added and the mixture was stirred at 0° C. for one hour. N-Methylmorpholine (44 μl) and isobutyl chloroformate (39 μl) were added to the reaction mixture, and the mixture was further stirred at 0° C. for 30 minutes. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate and filtered. Then, the filtrate was concentrated under reduced pressure. Tetrahydrofuran (2 ml) and water (0.4 ml) were added to the resulting residue. Then, sodium borohydride (15 mg) was added under ice-cooling, and the mixture was stirred at 0° C. for one hour. Methanol (2 ml) was added dropwise to the reaction mixture. Then, the mixture was returned to room temperature and stirred for 16 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, and then dried over sodium sulfate and filtered. Then, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel thin-layer chromatography (hexane-ethyl acetate) to obtain the title compound (16 mg, 27%) as an oil.

Workup

  1. stirringthe mixture was further stirred at 0° C. for 30 minutes
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationThen, the filtrate was concentrated under reduced pressure
  6. additionTetrahydrofuran (2 ml) and water (0.4 ml) were added to the resulting residue
  7. additionThen, sodium borohydride (15 mg) was added under ice-
  8. temperaturecooling
  9. stirringthe mixture was stirred at 0° C. for one hour
  10. additionMethanol (2 ml) was added dropwise to the reaction mixture
  11. customwas returned to room temperature
  12. stirringstirred for 16 hours
  13. additionWater was added to the reaction mixture
  14. extractionfollowed by extraction with ethyl acetate
  15. washThe organic layer was washed with brine
  16. dry with materialdried over sodium sulfate
  17. filtrationfiltered
  18. concentrationThen, the filtrate was concentrated under reduced pressure
  19. customThe resulting residue was purified by silica gel thin-layer chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-37845e8debd0497ea72885b7319f0f14
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

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