Hydrochloric Acid → HCID 68683529, compound

HRID 2234309Notes

Reaction equation

HRID 2234309 reaction equation
[Cl:1][C:2]1[C:3]([NH:24][C:25]2[N:35]=[C:34]3[C:28]([N:29]([CH3:42])[C:30](=[O:41])[CH2:31][CH2:32][N:33]3[CH:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)=[CH:27][N:26]=2)=[CH:4][C:5]([F:23])=[C:6]([CH:22]=1)[C:7]([NH:9][C@@H:10]1[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11]1)=[O:8].Cl.C(O)(C(F)(F)F)=O>O1CCOCC1>[Cl:1][C:2]1[C:3]([NH:24][C:25]2[N:35]=[C:34]3[C:28]([N:29]([CH3:42])[C:30](=[O:41])[CH2:31][CH2:32][N:33]3[CH:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)=[CH:27][N:26]=2)=[CH:4][C:5]([F:23])=[C:6]([CH:22]=1)[C:7]([NH:9][C@@H:10]1[CH2:14][CH2:13][NH:12][CH2:11]1)=[O:8]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 86617560HCID 86617560, compound

Product 1

HCID 68683529HCID 68683529, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

tert-butyl (3R)-3-[[5-chloro-4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-2-fluoro-benzoyl]amino]pyrrolidine-1-carboxylate (Example 324; 175 mg, 0.29 mmol) was dissolved in 1,4-dioxane (5 mL) and 4M HCl(aq) in 1,4-dioxane (10 mL) added. The mixture was stirred at room temperature for 2 hours. TFA (2 mL) was added an the reaction stirred for a further 1 hour. The reaction was concentrated, dissolved in DCM (10 mL) and TFA (3 mL) added. The reaction was stirred at room temperature for 1 hour, concentrated and the residue dissolved in methanol, absorbed on to an SCX column, washed with methanol and eluted with ammonia in methanol. Product containing fractions were combined and evaporated and the residue purified by column chromatography (7.5% ammonia in methanol/DCM) to yield the title compound as a white foam (112 mg, 77%).

Workup

  1. stirringstirred for a further 1 hour
  2. concentrationThe reaction was concentrated
  3. dissolutiondissolved in DCM (10 mL)
  4. additionTFA (3 mL) added
  5. stirringThe reaction was stirred at room temperature for 1 hour
  6. concentrationconcentrated
  7. dissolutionthe residue dissolved in methanol
  8. customabsorbed on to an SCX column
  9. washwashed with methanol
  10. washeluted with ammonia in methanol
  11. additionProduct containing fractions
  12. customevaporated
  13. customthe residue purified by column chromatography (7.5% ammonia in methanol/DCM)

Sources & evidence

ORD record
ord-4993d513214c4943a67cf74cb714b524
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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