Hydrochloric Acid → HCID 71544872, compound

HRID 1476793Notes

Reaction equation

HRID 1476793 reaction equation
N[C:2]1[CH:11]=[C:10]2[C:5]([C:6]3[C:23](=[O:24])[C:22]4[CH:21]=[C:20]([O:25][CH3:26])[CH:19]=[CH:18][C:17]=4[C:7]=3[N:8]([CH2:13][CH2:14][CH2:15][Br:16])[C:9]2=[O:12])=[CH:4][CH:3]=1.Cl.N([O-])=O.[Na+].[I-:32].[K+]>O1CCOCC1.O.[Cu]I>[Br:16][CH2:15][CH2:14][CH2:13][N:8]1[C:7]2[C:17]3[CH:18]=[CH:19][C:20]([O:25][CH3:26])=[CH:21][C:22]=3[C:23](=[O:24])[C:6]=2[C:5]2[C:10](=[CH:11][C:2]([I:32])=[CH:3][CH:4]=2)[C:9]1=[O:12]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 23668193Sodium NitriteHCID 71544871HCID 71544871, compound

Product 1

HCID 71544872HCID 71544872, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent3×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

3-Amino-6-(3-bromopropyl)-9-methoxy-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione (81, 420 mg, 1.01 mmol) was dissolved in dioxane (10 mL). Concentrated hydrochloric acid (0.65 mL, 3.3 mmol) was added and the reaction mixture was stirred for 10 min and then cooled down to 0° C. A solution of sodium nitrite (114 mg, 1.65 mmol) in water (5 mL) was slowly added with stirring while the temperature was −20° C. The reaction mixture was stirred for 30 min and then slowly added to a solution of copper (I) iodide (200 mg) and potassium iodide (300 mg) in water (15 mL). The reaction mixture was stirred at room temperature for 8 h and then heated at reflux for 1 h. The reaction mixture was diluted with water (200 mL) and extracted with chloroform (3×100 mL). The combined organic extracts were washed with an aqueous solution of sodium thiosulfate (2×200 mL), aqueous sodium bicarbonate (2×200 mL), water (100 mL) and brine (100 mL). The organic solution was dried over sodium sulfate and the solvent removed under vacuum. The residue was purified by silica gel column chromatography, eluting with chloroform-methanol, 30:1. Compound 82 was obtained as a dark red solid (402 mg, 76%): mp 207-209° C. IR (Film) 2922, 1765, 1655, 1599, 1532, 1478, 1455, 1430, 1379, 1295, 1225, 1047, 969, 812, 788, 691, 666, 592 cm−1; 1H NMR (CDCl3, 500 MHz) δ 8.60 (d, J=1.5 Hz, 1H), 8.32 (d, J=8.6 Hz, 1H), 7.93 (dd, J=8.5 Hz, J=1.5 Hz, 1H), 7.64 (d, J=8.4 Hz, 1H), 7.15 (d, J=2.3 Hz, 1H), 6.82 (dd, J=8.3 Hz, J=2.4 Hz, 1H), 4.58 (t, J=7.2 Hz, 2H), 3.89 (s, 3H), 3.64 (t, J=6.2 Hz, 2H), 2.44 (t, J=7.2 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 189.3, 162.5, 162.0, 156.6, 142.4, 137.6, 137.0, 131.4, 127.6, 124.7, 124.1, 123.9, 115.8, 111.1, 107.6, 91.2, 55.8, 44.2, 31.1, 30.2; ESIMS m/z (rel intensity) 523 (MH+, 60), 403 [(MH+—C3H6Br)+, 100]; HRESIMS m/z calcd for C20H15NO3IBr 523.9358 (MH+). found, 523.9362 (MH+).

Workup

  1. stirringwith stirring while the temperature
  2. customwas −20° C
  3. stirringThe reaction mixture was stirred for 30 min
  4. stirringThe reaction mixture was stirred at room temperature for 8 h
  5. temperatureheated
  6. temperatureat reflux for 1 h
  7. extractionextracted with chloroform (3×100 mL)
  8. washThe combined organic extracts were washed with an aqueous solution of sodium thiosulfate (2×200 mL), aqueous sodium bicarbonate (2×200 mL), water (100 mL) and brine (100 mL)
  9. dry with materialThe organic solution was dried over sodium sulfate
  10. customthe solvent removed under vacuum
  11. customThe residue was purified by silica gel column chromatography
  12. washeluting with chloroform-methanol, 30:1

Sources & evidence

ORD record
ord-9bed2cbe72834f00aba445c520584f4d
Source dataset
uspto-grants-2016_08
Patent number
US09402842B2

Reaction notes

Loading…