Acetic Anhydride → 1-(5-Carboxy-pentyl)-4-[5-(1-ethyl-3,3-dimethyl-5-phosphono-1,3-dihydro-indol-2-ylidene)-penta-1,3-dienyl]-quinolinium chloride

HRID 252796Notes

Reaction equation

HRID 252796 reaction equation
[CH2:1]([N+:3]1[C:11]2[C:6](=[CH:7][C:8]([P:12]([OH:15])([OH:14])=[O:13])=[CH:9][CH:10]=2)[C:5]([CH3:17])([CH3:16])[C:4]=1[CH3:18])[CH3:2].[CH:19]1[CH:24]=CC(N/C=C/C=NC2C=CC=CC=2)=C[CH:20]=1.[ClH:36].C(OC(=O)C)(=O)C.[I-].[C:45]([CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][N+:53]1[C:62]2[C:57](=[CH:58][CH:59]=[CH:60][CH:61]=2)[C:56]([CH3:63])=[CH:55][CH:54]=1)([OH:47])=[O:46].[OH-].[Na+].C(=O)(O)[O-].[Na+]>C(O)(=O)C.Cl.O.CO.N1C=CC=CC=1>[Cl-:36].[C:45]([CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][N+:53]1[C:62]2[C:57](=[CH:58][CH:59]=[CH:60][CH:61]=2)[C:56]([CH:63]=[CH:24][CH:19]=[CH:20][CH:18]=[C:4]2[C:5]([CH3:17])([CH3:16])[C:6]3[C:11](=[CH:10][CH:9]=[C:8]([P:12]([OH:14])([OH:15])=[O:13])[CH:7]=3)[N:3]2[CH2:1][CH3:2])=[CH:55][CH:54]=1)([OH:47])=[O:46]

Participants

12

Reactant 6

HCID 7918Acetic AnhydrideHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 5706364Benzenamine, N-(3-(phenylamino)-2-propen-1-ylidene)-, hydrochloride (1:?)HCID 593606011-ethyl-2,3,3-trimethyl-5-phosphono-3H-indoliumHCID 672626521-(5-Carboxy-pentyl)-4-methyl-quinolinium iodide

Product 1

HCID 866101851-(5-Carboxy-pentyl)-4-[5-(1-ethyl-3,3-dimethyl-5-phosphono-1,3-dihydro-indol-2-ylidene)-penta-1,3-dienyl]-quinolinium chloride

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolvent2×HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 1049PyridineSolvent

Conditions

Temperature
110 °C

Procedure

To a 50 mL flask were added 6 (0.25 g, 0.93 mmol), malonaldehyde dianilide hydrochloride (0.25 g, 0.97 mmol), acetic acid (4 mL) and acetic anhydride (4 mL). The mixture was heated at 110° C. for 90 min and then was cooled to rt. The volatile components were removed under vacuum to leave a tar. The tar was dissolved in acetic acid (4 mL) and then pyridine (5 mL) and 14 (0.34 g, 0.89 mmol) were added. The mixture was heated at 110° C. for 25 min and then cooled to rt. The volatile components were removed under vacuum to leave a dark blue tar that was dissolved in conc. HCl (20 mL). After stirring for 3 h, the mixture was diluted with water (150 mL) and then basified, first by addition of 4 M sodium hydroxide solution until the pH was approx. 4 and then with saturated sodium bicarbonate solution. The fluorescent product initially precipitated from the mixture but then re-dissolved. The aqueous solution was loaded onto a column of C-18 reverse-phase silica gel (4×15 cm) in water. The column was eluted with water to remove the salts and excess base, with 1 M HCl to generate the free acid of the fluorescent compound and then with water to remove the excess acid. Gradient elution from 0-55% methanol in water (5% steps of 500 mL-1 L) first eluted the symmetrical bisphosphonic acid fluorescent compound and then fluorescent compound 15. The fractions were evaporated in vacuo to leave a blue residue that was taken up in methanol (70 mL) and filtered through a medium frit. Water (30 mL) was added and then the solvent mixture was removed in vacuo to afford fluorescent compound 15 as a blue solid.

Workup

  1. temperaturewas cooled to rt
  2. customThe volatile components were removed under vacuum
  3. customto leave a tar
  4. temperatureThe mixture was heated at 110° C. for 25 min
  5. temperaturecooled to rt
  6. customThe volatile components were removed under vacuum
  7. customto leave a dark blue tar that
  8. customThe fluorescent product initially precipitated from the mixture
  9. dissolutionre-dissolved
  10. washThe column was eluted with water
  11. customto remove the salts and excess base
  12. customwith water to remove the excess acid
  13. washGradient elution from 0-55% methanol in water (5% steps of 500 mL-1 L)
  14. washfirst eluted the symmetrical bisphosphonic acid fluorescent compound
  15. customThe fractions were evaporated in vacuo
  16. customto leave a blue residue that
  17. filtrationfiltered through a medium frit
  18. additionWater (30 mL) was added
  19. customthe solvent mixture was removed in vacuo

Sources & evidence

ORD record
ord-b4c1174f88f64d8da147f367debd67b9
Source dataset
uspto-grants-2011_01
Patent number
US07868157B2

Reaction notes

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