Tetrahydrofuran → HCID 117667705, compound

HRID 712725Notes

Reaction equation

HRID 712725 reaction equation
[F:1][C:2]1[C:3]([C@@H:21](O)[CH3:22])=[C:4]([C:8]2[CH:9]=[C:10]3[C:15](=[N:16][CH:17]=2)[N:14]([C:18]([NH2:20])=[O:19])[CH2:13][CH2:12][CH2:11]3)[CH:5]=[N:6][CH:7]=1.C1COCC1.C1(OP([N:45]=[N+:46]=[N-:47])(=O)OC2C=CC=CC=2)C=CC=CC=1.C1CCN2C(=NCCC2)CC1>CCOC(C)=O.O>[N:45]([C@@H:21]([C:3]1[C:2]([F:1])=[CH:7][N:6]=[CH:5][C:4]=1[C:8]1[CH:9]=[C:10]2[C:15](=[N:16][CH:17]=1)[N:14]([C:18]([NH2:20])=[O:19])[CH2:13][CH2:12][CH2:11]2)[CH3:22])=[N+:46]=[N-:47]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 123414Diphenylphosphoryl azideHCID 86305760HCID 86305760, compound

Product 1

HCID 117667705HCID 117667705, compoundYield 82.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

6-[5-Fluoro-4-((S)-1-hydroxy-ethyl)-pyridin-3-yl]-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide (100 mg, 0.32 mmol), THF (1.4 mL) and phosphorazidic acid diphenyl ester (0.088 mL, 0.41 mmol) are combined and cooled to 0° C. DBU (0.061 mL, 0.41 mmol) is added dropwise. After 10 minutes, the reaction is warmed to room temperature for 18 hrs. The reaction mixture is diluted with EtOAc and water. The layers are separated. The aqueous layer is extracted with EtOAc. The combined organic layers are washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo to the crude product. Purification by flash column chromatography affords 90 mg of 6-[4-((R)-1-azido-ethyl)-5-fluoro-pyridin-3-yl]-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide.

Workup

  1. temperaturethe reaction is warmed to room temperature for 18 hrs
  2. customThe layers are separated
  3. extractionThe aqueous layer is extracted with EtOAc
  4. washThe combined organic layers are washed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to the crude product
  8. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-bba2048360944c9eb1ed0f6b96fe727a
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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