Malic Acid → HCID 178507297, compound

HRID 968886Notes

Reaction equation

HRID 968886 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([NH2:8])[N:3]=1.[S:9](=[O:13])(=[O:12])([OH:11])[OH:10].C(O)(=O)[CH:15]([CH2:17][C:18](O)=O)[OH:16]>[Cl-].[Na+].O>[S:9](=[O:11])(=[O:10])([OH:13])[OH:12].[NH2:1][C:2]1[CH:7]=[CH:6][C:5]2[C:4](=[N:8][C:15]([OH:16])=[CH:17][CH:18]=2)[N:3]=1

Participants

5

Reactant 3

HCID 525Malic AcidHCID 1118Sulfuric AcidHCID 88612,6-Diaminopyridine2×

Product 1

HCID 178507297HCID 178507297, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
45 °C

Procedure

2,6-Diaminopyridine (167 g, 1.53 mol) was added in portions to sulfuric acid (1.14 kg, 11.7 mol) at 40° C. The temperature of the solution was maintained at 40-50° C. during the addition with a water bath. When all of the 2,6-diaminopyridine was dissolved, the solution was cooled to 20° C. Malic acid (206 g, 1.53 mol) was added to the solution and the reaction mixture was gradually heated to 110° C. over 90 minutes. The mixture was stirred at 110-120° C. for one hour, cooled to room temperature, and poured slowly into a cold brine solution (167 g NaCl, 1.6 kg ice water). The quenched mixture was stirred at room temperature for one hour and filtered. The material was washed with hexanes (335 mL) and dried at 60° C. under vacuum to yield 2-amino-7-hydroxy-1,8-naphthyridine sulfuric acid salt as a yellow solid: 354 g, 89% yield; MS (DCI) M+1 at 162, 100%; 1H NMR (200 MHz, DMSO-d6) δ 4.32 (br. s, 5H, —OH, —NH2, H2SO4), 6.41 (d, J=9.0 Hz, 1H, C6), 6.56 (d J=9.0 Hz, 1H, C5), 7.85 (d J=6.6 Hz, 1H, C3), 7.91 (d J=6.6 Hz, 1H, C4).

Workup

  1. temperaturethe solution was cooled to 20° C
  2. temperaturethe reaction mixture was gradually heated to 110° C. over 90 minutes
  3. temperaturecooled to room temperature
  4. stirringThe quenched mixture was stirred at room temperature for one hour
  5. filtrationfiltered
  6. washThe material was washed with hexanes (335 mL)
  7. customdried at 60° C. under vacuum

Sources & evidence

ORD record
ord-f99dc7df061d4135893a5309c1ee424f
Source dataset
uspto-grants-2007_12
Patent number
US07304158B2

Reaction notes

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