Hydrogen Bromide → HCID 58349496, compound

HRID 2090062Notes

Reaction equation

HRID 2090062 reaction equation
N[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([Cl:13])[N:6]=[C:7]2[CH3:12].N([O-])=O.[Na+].[NH4+].[OH-].[BrH:20]>O>[Br:20][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([Cl:13])[N:6]=[C:7]2[CH3:12]

Participants

6

Reactant 4

HCID 260Hydrogen Bromide2×HCID 14923Ammonium HydroxideHCID 23668193Sodium NitriteHCID 58349459HCID 58349459, compound

Product 1

HCID 58349496HCID 58349496, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 5-amino-3-chloro-1-methylisoquinoline (460 mg, 2.4 mmol) in HBr (48%, 6 mL) and water (3 mL) at 0° C. was added slowly NaNO2 (165 mg, 2.4 mmol) in water (3 mL). The reaction was stirred at 0° C. for 10 minutes, then the excess NaNO2 was quenched by addition of a small amount of urea. The diazonium solution was then added slowly to a stirred solution of CuBr (411 mg, 2.9 mmol) in HBr (48%, 4 mL) at 75° C. The mixture was stirred for an additional 5 minutes at 75° C., then at room temperature for 18 hours. The mixture was poured onto crushed ice, adjusted to pH 9 with NH4OH, then extracted with EtOAc. The combined organics were washed with water then saturated NaCl (aq), dried over Na2SO4, filtered, then concentrated. The residue was purified by silica gel chromatography eluting with 10% EtOAc/hexanes to afford the title compound: 1H NMR (500 MHz, CDCl3): δ 8.09 (d, J=6.0 Hz, 1H), 7.98 (d, J=6.0 Hz, 1H); 7.97 (s, 1H), 7.44 (t, J=6.0 Hz, 1H); 2.98 (s, 3H). LC1: 2.68 min, (M+H): 256.

Workup

  1. customthe excess NaNO2 was quenched by addition of a small amount of urea
  2. stirringThe mixture was stirred for an additional 5 minutes at 75° C.
  3. waitat room temperature for 18 hours
  4. additionThe mixture was poured
  5. customonto crushed ice
  6. extractionextracted with EtOAc
  7. washThe combined organics were washed with water
  8. dry with materialsaturated NaCl (aq), dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel chromatography
  12. washeluting with 10% EtOAc/hexanes

Sources & evidence

ORD record
ord-038407e03e5541e8984ab1cef07b687b
Source dataset
uspto-grants-2013_05
Patent number
US08436015B2

Reaction notes

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