Water → 1,1-dimethylethyl {1-[((4R/S)-8-chloro-3-fluoro-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-4-piperidinyl}carbamate

HRID 15162

Reaction equation

HRID 15162 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]([Cl:26])[C:24](=[O:25])[N:15]([C:16]=43)[CH2:14]2)(=O)=O)=CC=1.[NH:29]1[CH2:34][CH2:33][CH:32]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:31][CH2:30]1.[Na].O>C(O)C>[Cl:26][C:23]1[C:24](=[O:25])[N:15]2[CH2:14][C:13]([CH2:12][N:29]3[CH2:30][CH2:31][CH:32]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:40])([CH3:39])[CH3:41])[CH2:33][CH2:34]3)([OH:28])[C:17]3=[C:18]([F:27])[CH:19]=[N:20][C:21]([CH:22]=1)=[C:16]23

Participants

6

Reactant 4

HCID 962WaterHCID 7238334-(N-Boc-amino)piperidine2×HCID 5360545Sodium2×HCID 131728166((4R/S)-8-chloro-3-fluoro-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 1317281651,1-dimethylethyl {1-[((4R/S)-8-chloro-3-fluoro-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

To a solution of crude ((4R/S)-8-chloro-3-fluoro-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl 4-methylbenzenesulfonate (˜2.5 g, assumed 6.10 mmol) in ethanol (50 mL), at room temperature, under argon was added 1,1-dimethylethyl 4-piperidinylcarbamate (1.22 g, 6.10 mmol) and sodium hydrogenocarbonate (1.94 g, 18.31 mmol). The reaction mixture was stirred for 8 hours. A further 0.5 equivalent of 1,1-dimethylethyl 4-piperidinylcarbamate (0.61 g, 3.05 mmol) and 1.5 equivalent of sodium hydrogenocarbonate (0.97 g, 9.15 mmol) were added. The reaction mixture was stirred for an additional 18 hours, treated with water (200 mL) and extracted with a 10% solution of methanol in dichloromethane (3×200 mL). The combined organic layers were dried over magnesium sulphate, evaporated and chromatograped affording an impure material which used crude in the following step.

Workup

  1. stirringThe reaction mixture was stirred for an additional 18 hours
  2. extractionextracted with a 10% solution of methanol in dichloromethane (3×200 mL)
  3. dry with materialThe combined organic layers were dried over magnesium sulphate
  4. customevaporated
  5. customchromatograped affording an impure material which

Sources & evidence

ORD record
ord-323d18e133644929a3f0562873857d2c
Source dataset
uspto-grants-2010_06
Patent number
US07732460B2

Linked notes

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