O-Phenylenediamine → (1-Aminomethyl-6,8-dimethoxy-isoquinolin-4-yl)-(1h-benzoimidazol-2-yl)-amine

HRID 14693

Reaction equation

HRID 14693 reaction equation
C([N:3]([CH2:6][CH3:7])[CH2:4]C)C.C(Cl)(Cl)=S.[NH2:12][C:13]1[C:22]2[C:17](=[C:18]([O:25][CH3:26])[CH:19]=[C:20]([O:23][CH3:24])[CH:21]=2)[C:16]([CH2:27][N:28]2C(=O)C3C(=CC=CC=3)C2=O)=[N:15][CH:14]=1.[C:39]1(N)[CH:44]=[CH:43]C=C[C:40]=1[NH2:45]>ClCCl.[Hg]=O>[NH2:28][CH2:27][C:16]1[C:17]2[C:22](=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=2[O:25][CH3:26])[C:13]([NH:12][C:4]2[NH:3][C:6]3[CH:7]=[CH:43][CH:44]=[CH:39][C:40]=3[N:45]=2)=[CH:14][N:15]=1

Participants

7

Reactant 4

HCID 7243O-PhenylenediamineHCID 8471TriethylamineHCID 10040ThiophosgeneHCID 593410902-(4-Amino-6,8-dimethoxy-isoquinolin-1-ylmethyl)-isoindole-1,3-dione

Product 1

HCID 46847539(1-Aminomethyl-6,8-dimethoxy-isoquinolin-4-yl)-(1h-benzoimidazol-2-yl)-amineYield 50.6%

Reagents, catalysts & solvents 2

HCID 30856Mercuric oxideCatalystHCID 6344DichloromethaneSolvent

Procedure

Triethylamine (210 μL, 1.52 mmol) and then thiophosgene (55 μL, 0.72 mmol) were added to a solution of Example 45C (200 mg, 0.55 mol) in dichloromethane (5 mL), and the reaction stirred 1 h at r.t. Organics were washed with 0.5 N HCl and brine, dried (MgSO4), and concentrated. The residue was dissolved in DMF (5 mL). Phenylenediamine (89 mg, 0.82 mmol) was added, and the reaction stirred at 90° C. for 2 h. Mercury(II) oxide was added, and the reaction stirred for 3 h longer before it was concentrated in vacuo. Deprotection was carried out in ethanol (5 mL) with hydrazine (0.2 mL) at r.t. for 1 h. Purification by Prep-HPLC gave 145 mg (46%) of the title compound (TFA salt) as a yellow solid. H1-NMR (MeOD-d4): δ 8.61 (s, 1H), 7.38-7.42 (m, 2H), 7.30-7.34 (m, 2H), 7.23 (s, 1H); 7.02 (d, 1H, J=2.0 Hz), 6.89 (d, 1H, J=2.0 Hz), 4.92 (s, 2H), 4.01 (s, 3H), 3.91 (s, 3H). MS (ES) (M+H) calc'd for C19H19N5O2, 350; found 350.

Workup

  1. washOrganics were washed with 0.5 N HCl and brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in DMF (5 mL)
  5. stirringthe reaction stirred at 90° C. for 2 h
  6. stirringthe reaction stirred for 3 h longer before it
  7. concentrationwas concentrated in vacuo
  8. waitDeprotection was carried out in ethanol (5 mL) with hydrazine (0.2 mL) at r.t. for 1 h
  9. customPurification by Prep-HPLC

Sources & evidence

ORD record
ord-ef59f10e08574a5fb9503363bad1cfd1
Source dataset
uspto-grants-2010_06
Patent number
US07732446B1

Linked notes

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