Trifluoroacetic acid → 4-{[cis-3-(aminomethyl)-4-hydroxy-1-piperidinyl]methyl}-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

HRID 15341Notes

Reaction equation

HRID 15341 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]2[CH:6]=[CH:7][C:8](=[O:27])[N:9]3[CH2:13][CH:12]([CH2:14][N:15]4[CH2:20][CH2:19][C@H:18]([OH:21])[C@H:17]([CH2:22][NH:23]C(=O)[O-])[CH2:16]4)[C:11]=1[C:10]=23.FC(F)(F)C(O)=O>ClCCl>[NH2:23][CH2:22][C@H:17]1[C@@H:18]([OH:21])[CH2:19][CH2:20][N:15]([CH2:14][CH:12]2[C:11]3=[C:2]([F:1])[CH:3]=[N:4][C:5]4[CH:6]=[CH:7][C:8](=[O:27])[N:9]([C:10]=43)[CH2:13]2)[CH2:16]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86630582{(cis-1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-4-hydroxy-3-piperidinyl}methyl)carbamate

Product 1

HCID 686844234-{[cis-3-(aminomethyl)-4-hydroxy-1-piperidinyl]methyl}-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-oneYield 59.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 1,1-dimethylethyl({(cis-1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-4-hydroxy-3-piperidinyl}methyl)carbamate (0.175 g, 0.405 mmol) in dichloromethane (2 ml) was treated with trifluoroacetic acid (1 ml) and stirred at room temperature for 20 min. The reaction mixture was evaporated and then redissolved using a 4:1 dichloromethane:methanol solution. The organic phase was then treated with aqueous sodium bicarbonate solution. The aqueous phase was extracted 10 times with a 4:1 dichloromethane:methanol solution and then the combined organic phases were dried and the solvent was removed under reduced pressure and the residue was subjected to column chromatography on silica gel using a dichloromethane, methanol and ammonia gradient to provide the desired compound (0.08 g).

Workup

  1. customThe reaction mixture was evaporated
  2. dissolutionredissolved
  3. additionThe organic phase was then treated with aqueous sodium bicarbonate solution
  4. extractionThe aqueous phase was extracted 10 times with a 4:1 dichloromethane
  5. dry with materialmethanol solution and then the combined organic phases were dried
  6. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-dffa17a8d0c4468ba2674302e125925d
Source dataset
uspto-grants-2010_06
Patent number
US07732461B2

Reaction notes

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