Trifluoroacetic acid → HCID 178473812, compound

HRID 1963958Notes

Reaction equation

HRID 1963958 reaction equation
[Cl:1][C:2]1[C:3]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([N:32]([C@H]3CCCNC3)[CH3:33])[N:27]=2)=[CH:4][C:5]([NH:8][C@H:9]2[CH2:14][CH2:13][C@H:12]([NH:15]C(=O)OCC3C=CC=CC=3)[CH2:11][CH2:10]2)=[N:6][CH:7]=1.C(O[C:44](=[O:46])[CH3:45])(=O)C.[C:47](O)([C:49](F)(F)F)=O>[Pd].C(Cl)Cl.CO>[NH2:15][C@H:12]1[CH2:13][CH2:14][C@H:9]([NH:8][C:5]2[CH:4]=[C:3]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([NH:32][CH2:33][C@H:49]4[CH2:47][CH2:4][CH2:5][N:6]([C:44](=[O:46])[CH3:45])[CH2:7]4)[N:27]=3)[C:2]([Cl:1])=[CH:7][N:6]=2)[CH2:10][CH2:11]1

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7918Acetic AnhydrideHCID 178482137HCID 178482137, compound

Product 1

HCID 178473812HCID 178473812, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of benzyl trans-4-(5′-chloro-6-((S)-piperidin-3-yl-methylamino)-2,4′-bipyridin-2′-yl-amino)cyclohexylcarbamate (15 mg, 0.027 mmol), DCM (2 mL), TEA (0.011 mL, 0.082 mmol) and acetic anhydride (3.09 μL, 0.033 mmol) was stirred at ambient temperature for 2 hours and the reaction progress was followed by LCMS. The solvent was concentrated off. The reaction mixture flask was flushed with argon, 10% palladium on activated carbon (5 mg, 4.70 μmol) was added and followed by careful addition of MeOH (0.8 mL). The resulting mixture was stirred under hydrogen for 45 minutes at ambient temperature and monitored by LCMS. To the crude reaction mixture was added 2 ml of DCM, filtered and the solvent was concentrated off. The resulting residue was dissolved in 1.0 ml of DMSO, filtered and purified by prep HPLC to give two fractions corresponding to the two title compounds respectively. After lyophilization, 4.0 mg of 1-((R)-3-((2′-(trans-4-aminocyclohexylamino)-5′-chloro-2,4′-bipyridin-6-yl-amino)methyl)piperidin-1-yl)ethanone, was obtained as a TFA salt. LCMS (m/z): 457.2 (MH+), retention time=0.46 min. In addition, 1.0 mg of 1-((R)-3-((2′-(trans-4-aminocyclohexylamino)-2,4′-bipyridin-6-yl-amino)methyl)piperidin-1-yl)ethanone, as TFA salt was also obtained. LCMS (m/z): 423.2 (MH+), retention time=0.45 min. This reaction yielded two products which are separated and purified by HPLC.

Workup

  1. concentrationThe solvent was concentrated off
  2. additionwas added
  3. stirringThe resulting mixture was stirred under hydrogen for 45 minutes at ambient temperature
  4. customTo the crude reaction mixture
  5. filtrationfiltered
  6. concentrationthe solvent was concentrated off
  7. dissolutionThe resulting residue was dissolved in 1.0 ml of DMSO
  8. filtrationfiltered
  9. custompurified by prep HPLC
  10. customto give two fractions corresponding to the two title compounds respectively

Sources & evidence

ORD record
ord-46238970d4194f40a6f9b11dc82cd8c0
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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