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

HRID 15315Notes

Reaction equation

HRID 15315 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]2[CH:6]=[CH:7][C:8](=[O:29])[N:9]3[CH2:13][CH:12]([CH2:14][N:15]4[CH2:20][CH2:19][CH:18]([NH:21]C(=O)OC(C)(C)C)[CH2:17][CH2:16]4)[C:11]=1[C:10]=23.C(O)(C(F)(F)F)=O>ClCCl>[NH2:21][CH:18]1[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:29])[N:9]([C:10]=43)[CH2:13]2)[CH2:16][CH2:17]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866305801,1-Dimethylethyl {1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-4-piperidinyl}carbamate

Product 1

HCID 686864184-[(4-Amino-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-oneYield 80.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1,1-dimethylethyl {1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-4-piperidinyl}carbamate (13.35 g, containing about 12.5% dichloromethane) in dichloromethane (125 ml) was ice-cooled, treated with TFA (100 ml), stirred at room temperature for 1 hour and evaporated. The residue was shaken with aqueous sodium bicarbonate (excess) and 15% methanol/dichloromethane, separated and the aqueous extracted about 50 times with 15% methanol/dichloromethane. The combined organic phases were dried and evaporated and the residue chromatographed using dichloromethane/methanol/0.88 ammonia 9:1:0.1 to give the product (8.1 g).

Workup

  1. temperaturecooled
  2. customevaporated
  3. stirringThe residue was shaken with aqueous sodium bicarbonate (excess) and 15% methanol/dichloromethane
  4. customseparated
  5. extractionthe aqueous extracted about 50 times with 15% methanol/dichloromethane
  6. customThe combined organic phases were dried
  7. customevaporated
  8. customthe residue chromatographed

Sources & evidence

ORD record
ord-4133a6cbf05b4f38b18877297229180d
Source dataset
uspto-grants-2010_06
Patent number
US07732461B2

Reaction notes

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