Sodium Iodide → (R)-8-chloro-3-(2-(3-fluoropyrrolidin-1-yl)ethoxy)-1,5-naphthyridine

HRID 2176661Notes

Reaction equation

HRID 2176661 reaction equation
Cl.[F:2][C@@H:3]1[CH2:7][CH2:6][NH:5][CH2:4]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:15][CH2:16][O:17][C:18]1[CH:19]=[N:20][C:21]2[C:26]([CH:27]=1)=[N:25][CH:24]=[CH:23][C:22]=2[Cl:28].[I-].[Na+]>CN(C=O)C>[Cl:28][C:22]1[CH:23]=[CH:24][N:25]=[C:26]2[C:21]=1[N:20]=[CH:19][C:18]([O:17][CH2:16][CH2:15][N:5]1[CH2:6][CH2:7][C@@H:3]([F:2])[CH2:4]1)=[CH:27]2

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 2759162(3R)-3-fluoropyrrolidine hydrochlorideHCID 576909903-(2-Bromoethoxy)-8-chloro-1,5-naphthyridine

Product 1

HCID 57690911(R)-8-chloro-3-(2-(3-fluoropyrrolidin-1-yl)ethoxy)-1,5-naphthyridineYield 54%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 25 mL round bottom flask at rt was charged with (R)-3-fluoropyrrolidine hydrochloride (124 mg, 0.99 mmol). To this was added potassium carbonate (365 mg, 2.64 mmol), 3-(2-bromoethoxy)-8-chloro-1,5-naphthyridine (190 mg, 0.66 mmol), sodium iodide (149 mg, 0.99 mmol) and DMF (2 mL). Reaction mixture placed in oil bath preheated to 60° C. and allowed to stir for 16 hrs. Reaction mixture passed through celite cake, rinsed with 10% MeOH/DCM and filtrate concentrated to afford yellow oil. This was purified by ISCO silica gel chromatography (20-40% EtOAC/Hexanes) to afford (R)-8-chloro-3-(2-(3-fluoropyrrolidin-1-yl)ethoxy)-1,5-naphthyridine (105 mg, 54% yield). MS [M+H]=296.2. Calc'd for C14H15ClFN3O=295.7.

Workup

  1. customReaction mixture
  2. customplaced in oil bath
  3. custompreheated to 60° C.
  4. customReaction mixture
  5. washrinsed with 10% MeOH/DCM and filtrate
  6. concentrationconcentrated
  7. customto afford yellow oil
  8. customThis was purified by ISCO silica gel chromatography (20-40% EtOAC/Hexanes)

Sources & evidence

ORD record
ord-1440c86920a644c8b70a11a08217f2af
Source dataset
uspto-grants-2015_06
Patent number
US09066954B2

Reaction notes

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