Sodium Carbonate → 1,1-dimethylethyl (1-{[3,8-difluoro-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl]methyl}-4-piperidinyl)carbamate

HRID 15139Notes

Reaction equation

HRID 15139 reaction equation
CC1C=CC(S(O[CH2:12][C:13]2([OH:28])[C:17]3=[C:18]([F:27])[CH:19]=[N:20][C:21]4[CH:22]=[C:23]([F:26])[C:24](=[O:25])[N:15]([C:16]=43)[CH2:14]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[NH:35]1[CH2:40][CH2:39][CH:38]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:37][CH2:36]1>C(O)C>[F:27][C:18]1[CH:19]=[N:20][C:21]2[CH:22]=[C:23]([F:26])[C:24](=[O:25])[N:15]3[CH2:14][C:13]([CH2:12][N:35]4[CH2:36][CH2:37][CH:38]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:46])([CH3:45])[CH3:47])[CH2:39][CH2:40]4)([OH:28])[C:17]=1[C:16]=23

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 7238334-(N-Boc-amino)piperidineHCID 86614148[3,8-difluoro-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl]methyl 4-methylbenzenesulfonate

Product 1

HCID 866141491,1-dimethylethyl (1-{[3,8-difluoro-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl]methyl}-4-piperidinyl)carbamate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of crude [3,8-difluoro-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl]methyl 4-methylbenzenesulfonate (1.2 g, 2.79 mmol) in ethanol (40 mL) was treated with sodium carbonate (889 mg, 8.38 mmol) and 1,1-dimethylethyl 4-piperidinylcarbamate (615 mg, 3.07 mmol). The reaction mixture was stirred at room temperature for 18 hours under argon, evaporated and treated with water (200 mL). The aqueous layer was extracted with a 10% solution of methanol in dichloromethane (3×200 mL) and the combined organic extracts dried over magnesium sulphate and evaporated. The residue was chromatographed eluting with a 0-10% gradient of methanol in dichloromethane affording a yellow solid (1.1 g, 91%).

Workup

  1. customevaporated
  2. additiontreated with water (200 mL)
  3. extractionThe aqueous layer was extracted with a 10% solution of methanol in dichloromethane (3×200 mL)
  4. dry with materialthe combined organic extracts dried over magnesium sulphate
  5. customevaporated
  6. customThe residue was chromatographed
  7. washeluting with a 0-10% gradient of methanol in dichloromethane affording a yellow solid (1.1 g, 91%)

Sources & evidence

ORD record
ord-d95809ec6f3149dd8b3e41f27e2a93c7
Source dataset
uspto-grants-2010_06
Patent number
US07732460B2

Reaction notes

Loading…