Trifluoroacetic acid → HCID 16070095, compound

HRID 1864007Notes

Reaction equation

HRID 1864007 reaction equation
[NH2:1][C:2]1[C:3]([C:7]2[N:8]([CH2:37][CH3:38])[C:9]3[C:14]([O:15][CH2:16][C@H:17]4[O:22][CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18]4)=[CH:13][N:12]=[C:11]([C:30]#[C:31][C:32]([OH:35])([CH3:34])[CH3:33])[C:10]=3[N:36]=2)=[N:4][O:5][N:6]=1.FC(F)(F)C(O)=O.[OH-].[Na+]>C(Cl)Cl.O>[NH2:1][C:2]1[C:3]([C:7]2[N:8]([CH2:37][CH3:38])[C:9]3[C:14]([O:15][CH2:16][C@H:17]4[O:22][CH2:21][CH2:20][NH:19][CH2:18]4)=[CH:13][N:12]=[C:11]([C:30]#[C:31][C:32]([CH3:33])([OH:35])[CH3:34])[C:10]=3[N:36]=2)=[N:4][O:5][N:6]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 86619283HCID 86619283, compound

Product 1

HCID 16070095HCID 16070095, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

To a suspension of 1,1-Dimethylethyl (2S)-2-({[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-4-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-imidazo[4,5-c]pyridin-7-yl]oxy}methyl)-4-morpholinecarboxylate (14.2 g, 0.027 mol) in methylene chloride (150 mL) was added trifluoroacetic acid (40 mL). After 1 h, the solvent was removed in vacuo. The residue was evaporated from ethyl acetate (2×) to give a solid. The residue was suspended in water and treated with 1N NaOH in an ice bath until the mixture was basic (pH 8). The precipitate was isolated by filtration, washed with water, ethyl acetate and dried in a vacuum oven at 40° C. for 4 h. The resulting solid was treated with ethyl acetate (250 ml) and stirred at 65° C. then allowed to cool to RT and then placed in an ice bath and then filtered and the solid dried in a vacuum oven at 40° C. The resulting solid was suspended in 20% tetrahydrofuran/ethanol (1.2 L). Darco G60 activated charcoal (3.9 g) was added and the mixture heated at reflux for 90 min. and filtered while hot through celite. The solvent was removed and retreated with ethanol and removed in vacuo (2×). The resulting solid was dried under high vacuum for 24 hr at 40° C. to afford the title compound (7.24 g, 64%). MS (ES)+ m/e 428 [M+H]+.

Workup

  1. customthe solvent was removed in vacuo
  2. customThe residue was evaporated from ethyl acetate (2×)
  3. customto give a solid
  4. customThe precipitate was isolated by filtration
  5. washwashed with water, ethyl acetate
  6. customdried in a vacuum oven at 40° C. for 4 h
  7. additionThe resulting solid was treated with ethyl acetate (250 ml)
  8. temperatureto cool to RT
  9. customplaced in an ice bath
  10. filtrationfiltered
  11. customthe solid dried in a vacuum oven at 40° C
  12. additionDarco G60 activated charcoal (3.9 g) was added
  13. temperaturethe mixture heated
  14. temperatureat reflux for 90 min.
  15. filtrationfiltered while hot through celite
  16. customThe solvent was removed
  17. customremoved in vacuo (2×)
  18. customThe resulting solid was dried under high vacuum for 24 hr at 40° C.

Sources & evidence

ORD record
ord-f1faa3a4c50e42ffad927efaa7d830d6
Source dataset
uspto-grants-2009_12
Patent number
US07625890B2

Reaction notes

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