Hydrochloric Acid → (4R/S)-4-[(4-amino-1-piperidinyl)methyl]-8-chloro-3-fluoro-4-hydroxy-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

HRID 15163Notes

Reaction equation

HRID 15163 reaction equation
[Cl:1][C:2]1[C:3](=[O:31])[N:4]2[CH2:14][C:13]([CH2:16][N:17]3[CH2:22][CH2:21][CH:20]([NH:23]C(=O)OC(C)(C)C)[CH2:19][CH2:18]3)([OH:15])[C:6]3=[C:7]([F:12])[CH:8]=[N:9][C:10]([CH:11]=1)=[C:5]23.Cl>ClCCl.CO.O1CCOCC1>[NH2:23][CH:20]1[CH2:19][CH2:18][N:17]([CH2:16][C:13]2([OH:15])[C:6]3=[C:7]([F:12])[CH:8]=[N:9][C:10]4[CH:11]=[C:2]([Cl:1])[C:3](=[O:31])[N:4]([C:5]=43)[CH2:14]2)[CH2:22][CH2:21]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 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

Product 1

HCID 23634272(4R/S)-4-[(4-amino-1-piperidinyl)methyl]-8-chloro-3-fluoro-4-hydroxy-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A solution of crude 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 (˜1 g, 2 mmol) in dichloromethane/methanol (20 mL/20 mL) was treated with a 4M solution of HCl in 1,4-dioxane ((20 mL) was stirred at room temperature, under argon, for 30 min. The reaction mixture was evaporated, dissolved in water (˜10 mL), basified by addition of solid sodium carbonate and evaporated. The residue was stirred with a 15% solution of methanol in dichloromethane (3×200 mL). The combined organic layers were dried over magnesium sulphate, evaporated and chromatographed eluting with a gradient of dichloromethane and 2M ammonia/methanol affording the product (215 mg, 27%).

Workup

  1. customThe reaction mixture was evaporated
  2. dissolutiondissolved in water (˜10 mL)
  3. additionbasified by addition of solid sodium carbonate
  4. customevaporated
  5. stirringThe residue was stirred with a 15% solution of methanol in dichloromethane (3×200 mL)
  6. dry with materialThe combined organic layers were dried over magnesium sulphate
  7. customevaporated
  8. customchromatographed
  9. washeluting with a gradient of dichloromethane and 2M ammonia/methanol affording the product (215 mg, 27%)

Sources & evidence

ORD record
ord-245814fc2f9d4bc6ae63012de1bb8dee
Source dataset
uspto-grants-2010_06
Patent number
US07732460B2

Reaction notes

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