Sodium Nitrite → HCID 24959703, compound

HRID 336715Notes

Reaction equation

HRID 336715 reaction equation
N[C:2]1[N:11]=[C:10]([C:12]2[CH:21]=[C:20]([CH3:22])[C:15]([O:16][CH2:17][CH2:18][OH:19])=[C:14]([CH3:23])[CH:13]=2)[CH:9]=[C:8]2[C:3]=1[C:4]([O:26][CH3:27])=[CH:5][C:6]([O:24][CH3:25])=[N:7]2.N([O-])=[O:29].[Na+]>O.Cl>[OH:19][CH2:18][CH2:17][O:16][C:15]1[C:20]([CH3:22])=[CH:21][C:12]([C:10]2[NH:11][C:2](=[O:29])[C:3]3[C:4]([O:26][CH3:27])=[CH:5][C:6]([O:24][CH3:25])=[N:7][C:8]=3[CH:9]=2)=[CH:13][C:14]=1[CH3:23]

Participants

5

Reactant 2

HCID 23668193Sodium NitriteHCID 66661750HCID 66661750, compound

Product 1

HCID 24959703HCID 24959703, compoundYield 26.3%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

2-[4-(5-amino-2,4-dimethoxy-[1,6]naphthyridin-7-yl)-2,6-dimethyl-phenoxyl]-ethanol (0.302 g, 0.82 mmol) in water (5 mL) and conc. Hydrochloric acid (3 mL) were mixed with stirring. The reaction mixture was cooled to 0° C. and a solution of sodium nitrite (0.305 g, 4.42 mmol) in water (3 mL) was added dropwise. The reaction mixture was stirred at 0° C. for 40 min. To the reaction mixture was added 1 N hydrochloric acid (10 mL) and heated at 55° C. for 50 min and then stirred at room temperature overnight. The reaction mixture was extracted with dichloromethane and the aqueous layer was basified with aqueous 5% NaOH and saturated NaHCO3 solution. Water was evaporated and the organic compound was washed with a dichloromethane/methanol solution and concentrated to leave a crude which was purified by silica gel (50 g) column chromatography, employing 50% ethyl acetate in hexane and hexane/ethyl acetate/methanol (3:2:1) as eluent, to obtain 7-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-2,4-dimethoxy-1,6-naphthyridin-5(6H)-one (0.080 g, 26%). Selected data: MS (ES) m/z: 371.1; MP 224.9-225.4° C.

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 40 min
  2. temperatureheated at 55° C. for 50 min
  3. stirringstirred at room temperature overnight
  4. extractionThe reaction mixture was extracted with dichloromethane
  5. customWater was evaporated
  6. washthe organic compound was washed with a dichloromethane/methanol solution
  7. concentrationconcentrated
  8. customto leave a crude which
  9. customwas purified by silica gel (50 g) column chromatography

Sources & evidence

ORD record
ord-836cf0e002ee43b09582cb1f7d4b9178
Source dataset
uspto-grants-2014_11
Patent number
US08889698B2

Reaction notes

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