1,4-Dioxane → 4-{[cis-4-amino-3-fluoro-1-piperidinyl]methyl}3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

HRID 15334Notes

Reaction equation

HRID 15334 reaction equation
[F:1][C@H:2]1[C@@H:7]([NH:8]C(=O)OCC2C=CC=CC=2)[CH2:6][CH2:5][N:4]([CH2:19][CH:20]2[C:24]3=[C:25]([F:33])[CH:26]=[N:27][C:28]4[CH:29]=[CH:30][C:31](=[O:32])[N:22]([C:23]=43)[CH2:21]2)[CH2:3]1.O1CCOCC1>C(O)C.[Pd]>[NH2:8][C@H:7]1[CH2:6][CH2:5][N:4]([CH2:19][CH:20]2[C:24]3=[C:25]([F:33])[CH:26]=[N:27][C:28]4[CH:29]=[CH:30][C:31](=[O:32])[N:22]([C:23]=43)[CH2:21]2)[CH2:3][C@H:2]1[F:1]

Participants

5

Reactant 2

HCID 312751,4-DioxaneHCID 131728171racemic phenylmethyl {cis-3-fluoro-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 686856724-{[cis-4-amino-3-fluoro-1-piperidinyl]methyl}3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-oneYield 86.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A solution of racemic phenylmethyl {cis-3-fluoro-1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-4-piperidinyl}carbamate (1.218 g) in ethanol (20 ml)/1,4-dioxane (5 ml) was treated with 10% Pd/C (600 mg) and stirred under hydrogen at atmospheric pressure for 5 hours. After filtration through kieselguhr, the filtrate was evaporated and the residue chromatographed on silica gel, eluting with dichloromethane/methanol/0.88 aqueous ammonia, to give the desired compound (745 mg, 86%).

Workup

  1. filtrationAfter filtration through kieselguhr
  2. customthe filtrate was evaporated
  3. customthe residue chromatographed on silica gel
  4. washeluting with dichloromethane/methanol/0.88 aqueous ammonia

Sources & evidence

ORD record
ord-16a852f139f64e5b966f6e774f90d761
Source dataset
uspto-grants-2010_06
Patent number
US07732461B2

Reaction notes

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