Hydrochloric Acid → HCID 178508008, compound

HRID 219249Notes

Reaction equation

HRID 219249 reaction equation
Cl[C:2]1[CH:3]=[CH:4][N:5]=[C:6]2[C:11]=1[N:10]=[CH:9][C:8]([NH2:12])=[CH:7]2.ClC1C=CN=C2C=1N=CC(N=C(C1C=CC=CC=1)C1C=CC=CC=1)=C2.Cl.C(=O)(O)[O-:40].[Na+]>O1CCCC1>[NH2:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([OH:40])=[CH:3][CH:4]=[N:5]2)=[N:10][CH:9]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 576910588-chloro-N-(diphenylmethylene)-1,5-naphthyridin-3-amineHCID 576913478-Chloro-1,5-naphthyridin-3-amine

Product 1

HCID 178508008HCID 178508008, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

8-chloro-1,5-naphthyridin-3-amine. A round bottom flask under nitrogen was charged with 8-chloro-N-(diphenylmethylene)-1,5-naphthyridin-3-amine (315 mg, 0.92 mmol), 2M aqueous HCl (1.42 mL, 2.84 mmol), and tetrahydrofuran (0.25M, 3.67 mL). This was stirred at RT for 30 minutes. Reaction basified with aq. sodium bicarbonate solution and product extracted with dichloromethane. This was dried over sodium sulfate and concentrated to afford orange solid; which was purified via ISCO silica gel chromatography, 40 g column, 30% (90/10/1 DCM:MeOH:NH4OH)/DCM over 40 minutes to afford 7-amino-1,5-naphthyridin-4-ol (140 mg, 95% yield) as yellow solid. MS[M+H]=180.2. Calc'd for C8H6ClN3=179.6. 2) 8-chloro-N-(2-methoxyethyl)-1,5-naphthyridin-3-amine. A round bottom flask under nitrogen atmosphere was charged with 8-chloro-1,5-naphthyridin-3-amine (160 mg, 0.89 mmol), DMF (2.2 mL, 0.89 mmol). This was cooled to 0° C. and SODIUM HYDRIDE (60% dispersion in oil) (107 mg, 4.45 mmol) added portionwise. This was quickly followed by addition of 1-bromo-2-methoxyethane (0.12 mL, 1.25 mmol) dropwise via syringe. Ice bath removed and reaction mixture heated to 85° C. and stirred at this temperature for 16 hours. Reaction diluted with 5 mL of 5% MeOH/Dichloromethane, loaded onto silica gel column and eluted with 2% MeOH/DCM to afford 8-chloro-N-(2-methoxyethyl)-1,5-naphthyridin-3-amine (70 mg, 33% yield) as a light yellow solid. MS[M+H]=238.2. Calc'd for C11H12ClN3O=237.7.

Workup

  1. customReaction
  2. extractionextracted with dichloromethane
  3. dry with materialThis was dried over sodium sulfate
  4. concentrationconcentrated
  5. customto afford orange solid
  6. customwhich was purified via ISCO silica gel chromatography, 40 g column, 30% (90/10/1 DCM:MeOH:NH4OH)/DCM over 40 minutes

Sources & evidence

ORD record
ord-41ad1aef3ae64f7899899dc0d08d518b
Source dataset
uspto-grants-2012_06
Patent number
US08198448B2

Reaction notes

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