Trifluoroacetic acid → N-{(1S)-1-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-ylcarbonyl]-2,2-dimethylpropyl}-1H-indole-2-carboxamide

HRID 2098447Notes

Reaction equation

HRID 2098447 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([NH:12][C@H:13]([C:18]([N:20]1[CH2:25][C@@H:24]2[CH2:26][C@H:21]1[CH2:22][N:23]2C(OC(C)(C)C)=O)=[O:19])[C:14]([CH3:17])([CH3:16])[CH3:15])=[O:11].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C@H:21]12[CH2:26][C@H:24]([NH:23][CH2:22]1)[CH2:25][N:20]2[C:18]([C@@H:13]([NH:12][C:10]([C:2]1[NH:1][C:9]2[C:4]([CH:3]=1)=[CH:5][CH:6]=[CH:7][CH:8]=2)=[O:11])[C:14]([CH3:17])([CH3:16])[CH3:15])=[O:19]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 672151111,1-Dimethylethyl (1S,4S)-5-[N-(1H-indol-2-ylcarbonyl)-3-methyl-L-valyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

Product 1

HCID 67072627N-{(1S)-1-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-ylcarbonyl]-2,2-dimethylpropyl}-1H-indole-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl (1S,4S)-5-[N-(1H-indol-2-ylcarbonyl)-3-methyl-L-valyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (40.5 g, 89.2 mmol) in CH2Cl2 (300 mL) was added TFA (75 mL) at 0° C. The mixture was stirred at room temperature for 18 h. The reaction was quenched with 1N NaOH while adjusting the pH of the solution to 8-9. The reaction was then extracted with CH2Cl2 (3×500 mL), dried over Na2SO4, filtered, and concentrated to yield the crude product. LCMS (m/z): 355.3 (M+H).

Workup

  1. customThe reaction was quenched with 1N NaOH
  2. extractionThe reaction was then extracted with CH2Cl2 (3×500 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d9ad89bec1314d45b04a0b15f11b33cc
Source dataset
uspto-grants-2013_05
Patent number
US08450484B2

Reaction notes

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