Potassium Carbonate → HCID 178522778, compound

HRID 887329Notes

Reaction equation

HRID 887329 reaction equation
C([O:4][C:5]1[N:6]=[CH:7][C:8]2[C:13]([CH:14]=1)=[C:12]([NH2:15])[CH:11]=[CH:10][CH:9]=2)(=O)C.[Br:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][N:24]=[C:25]=[O:26])=[CH:19][CH:18]=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.C1COCC1>[Br:16][C:17]1[CH:18]=[CH:19][C:20]([CH2:23][NH:24][C:25]([NH:15][C:12]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:13]=2[CH:14]=[C:5]([OH:4])[N:6]=[CH:7]3)=[O:26])=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 43746174-Bromobenzyl isocyanateHCID 22337569HCID 22337569, compound

Product 1

HCID 178522778HCID 178522778, compound

Reagents, catalysts & solvents 1

HCID 22635083Tetrahydrofuran tolueneSolvent

Procedure

5-Amino-3-isoquinolinyl acetate in toluene:THF (5:1, 5 mL) was treated with 1-bromo-4-(isocyanatomethyl)benzene (105 mg). After stirring for 1 hour, the mixture was concentrated under reduced pressure and the residue dissolved in MeOH (20 mL) and treated with K2CO3 (4 eq) and stirred for 16 hours. The mixture was concentrated under reduced pressure and partitioned between CH2Cl2 and water. The aqueous phase was separated and the pH was adjusted to approximately 6 with HCl. The acidified solution was filtered, and the filter cake was dried. The solid was purified by reverse-phase chromatography (using TFA as eluent) to provide the title compound. MS (ESI+) m/z 374, 372 (M+H)+; MS (ESI−) m/z 372, 370 (M−H)−; 1H NMR (DMSO, 300 MHz) δ 4.33 (d, J 5.8, 2H), 7.06 (m, 1H), 7.29 (m, 3H), 7.57 (m, 3H), 8.07 (d, J 7.8, 1H), 8.48 (s, 1H), 8.80 (s, 1H), 8.87 (s, 1H); Anal. Calcd for C17H14BrN3O2+0.2 TFA: C, 53.08; H, 3.42; N, 10.43. Found: C, 52.91; H, 3.62; N, 10.43.

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. dissolutionthe residue dissolved in MeOH (20 mL)
  3. stirringstirred for 16 hours
  4. concentrationThe mixture was concentrated under reduced pressure
  5. custompartitioned between CH2Cl2 and water
  6. customThe aqueous phase was separated
  7. filtrationThe acidified solution was filtered
  8. customthe filter cake was dried
  9. customThe solid was purified by reverse-phase chromatography (using TFA as eluent)

Sources & evidence

ORD record
ord-a18aeda172044339819b07b814b84e77
Source dataset
uspto-grants-2012_08
Patent number
US08247413B2

Reaction notes

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