Triethylamine → 5-(1,1-dioxothiazinan-2-yl)-N-[[4-fluoro-2-(isopropylcarbamoyl)phenyl]methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide

HRID 2252813Notes

Reaction equation

HRID 2252813 reaction equation
[O:1]=[S:2]1(=[O:22])[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[N:17]=[C:16]([C:18](O)=[O:19])[C:15]([OH:21])=[C:14]2[C:9]=1[CH:10]=[CH:11][CH:12]=[N:13]2.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.[Cl-].[F:46][C:47]1[CH:52]=[CH:51][C:50]([CH2:53][NH3+:54])=[C:49]([C:55]([NH:57][CH:58]([CH3:60])[CH3:59])=[O:56])[CH:48]=1.C(N(CC)CC)C.[OH-].[Na+]>O.CN(C=O)C>[O:1]=[S:2]1(=[O:22])[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[N:17]=[C:16]([C:18]([NH:54][CH2:53][C:50]2[CH:51]=[CH:52][C:47]([F:46])=[CH:48][C:49]=2[C:55]([NH:57][CH:58]([CH3:60])[CH3:59])=[O:56])=[O:19])[C:15]([OH:21])=[C:14]2[C:9]=1[CH:10]=[CH:11][CH:12]=[N:13]2

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 596452235-(1,1-Dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxylic acidHCID 86600177{4-Fluoro-2-[(isopropylamino)carbonyl]phenyl}methanaminium chloride

Product 1

HCID 30134005-(1,1-dioxothiazinan-2-yl)-N-[[4-fluoro-2-(isopropylcarbamoyl)phenyl]methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-(1,1-Dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxylic acid (200 mg, 0.62 mmol, prepared as described in Example 3, Step 7), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (154 mg, 0.80 mmol), and 1-hydroxy-7-azabenzotriazole (109 mg, 0.80 mmol) were added to dry DMF (15 mL) and stirred for 30 minutes to preform the activated ester. {4-Fluoro-2-[(isopropylamino)carbonyl]phenyl}methanaminium chloride (168 mg, 0.68 mmol) and triethylamine (95 μL, 0.68 mmol) were added and the reaction was stirred overnight at room temperature. The reaction was poured into water, the pH was adjusted to ˜10 using 1N NaOH, and resulting solution was extracted several times with CHCl3. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to dryness in vacuo. The residue was redissolved in basic water and CHCl3, acidified to pH=4 using 1N HCl and extracted several times with CHCl3. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to a whitish solid. Methanol was added to the flask and the flask was sonicated for 5 minutes. The resulting solids were collected by vacuum filtration to give the title compound as an off-white solid.

Workup

  1. stirringthe reaction was stirred overnight at room temperature
  2. customresulting solution
  3. extractionwas extracted several times with CHCl3
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness in vacuo
  7. dissolutionThe residue was redissolved in basic water
  8. extractionextracted several times with CHCl3
  9. dry with materialThe combined organic extracts were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to a whitish solid
  12. additionMethanol was added to the flask
  13. customthe flask was sonicated for 5 minutes
  14. filtrationThe resulting solids were collected by vacuum filtration

Sources & evidence

ORD record
ord-21dac70422424639bc4edd648b008b0d
Source dataset
uspto-grants-2008_01
Patent number
US07323460B2

Reaction notes

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