Hydrochloric Acid → HCID 57886945, compound

HRID 1819320Notes

Reaction equation

HRID 1819320 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[C:5]([O:9][C:10]([NH:12][C@@H:13]1[CH2:18][CH2:17][CH2:16][N:15]([C:19]2[N:27]([CH2:28][C:29]3[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=3[Cl:36])[C:26]3[C:25](=[O:37])[N:24](CC4C=CC(OC)=CC=4)[C:23](=[O:47])[N:22]([CH3:48])[C:21]=3[C:20]=2[C:49]([O:51][CH3:52])=[O:50])[CH2:14]1)=[O:11])([CH3:8])([CH3:7])[CH3:6].Cl>C1(OC)C=CC=CC=1>[C:5]([O:9][C:10]([NH:12][C@@H:13]1[CH2:18][CH2:17][CH2:16][N:15]([C:19]2[N:27]([CH2:28][C:29]3[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=3[Cl:36])[C:26]3[C:25](=[O:37])[NH:24][C:23](=[O:47])[N:22]([CH3:48])[C:21]=3[C:20]=2[C:49]([O:51][CH3:52])=[O:50])[CH2:14]1)=[O:11])([CH3:8])([CH3:7])[CH3:6]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6451240Aluminum(III) ChlorideHCID 57886948HCID 57886948, compound

Product 1

HCID 57886945HCID 57886945, compoundYield 56.5%

Reagents, catalysts & solvents 1

HCID 7519AnisoleSolvent

Conditions

Temperature
65 °C

Procedure

Under a nitrogen atmosphere, a solution of aluminum chloride (395 mg) in anisole (1.5 ml) was added to methyl 6-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-5-(2-chloro-5-fluorobenzyl)-3-(4-methoxybenzyl)-1-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidine-7-carboxylate (260 mg), and the resulting mixture was stirred at 65° C. for 4 hours. After the reaction solution was cooled to 25° C., 1N hydrochloric acid was added thereto and the aqueous layer was washed with ethyl acetate. The aqueous layer was neutralized with a 1N aqueous sodium hydroxide solution and extracted with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered and the filtrate was concentrated under reduced pressure. To the resulting residue were added di-tert-butyl dicarbonate (415 mg), 1,4-dioxane (4 ml) and a saturated aqueous sodium hydrogencarbonate solution (4 ml) and the resulting mixture was stirred at 25° C. for 16 hours. Water was added to the reaction solution, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered and the filtrate was concentrated under reduced pressure. To the resulting residue was added diethyl ether/hexane and the resulting mixture was filtered and then washed with hexane to obtain the title compound (121 mg) as a light-yellow solid.

Workup

  1. temperatureAfter the reaction solution was cooled to 25° C.
  2. washthe aqueous layer was washed with ethyl acetate
  3. extractionextracted with chloroform
  4. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. additionTo the resulting residue were added di-tert-butyl dicarbonate (415 mg), 1,4-dioxane (4 ml)
  9. stirringa saturated aqueous sodium hydrogencarbonate solution (4 ml) and the resulting mixture was stirred at 25° C. for 16 hours
  10. additionWater was added to the reaction solution
  11. extractionfollowed by extraction with chloroform
  12. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  13. dry with materialdried over anhydrous sodium sulfate
  14. filtrationfiltered
  15. concentrationthe filtrate was concentrated under reduced pressure
  16. additionTo the resulting residue was added diethyl ether/hexane
  17. filtrationthe resulting mixture was filtered
  18. washwashed with hexane

Sources & evidence

ORD record
ord-17e74c7738284a798df74c66c5af1c38
Source dataset
uspto-grants-2009_10
Patent number
US07601728B2

Reaction notes

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