4-Chloroquinazoline → 7-(2-Methoxyethoxy)-4-(2-methyl-3-(quinazolin-4-ylamino)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361290Notes

Reaction equation

HRID 2361290 reaction equation
[NH2:1][C:2]1[C:3]([CH3:29])=[C:4]([C:8]2[C:20]3[C:19]4[C:14](=[CH:15][C:16]([O:21][CH2:22][CH2:23][O:24][CH3:25])=[CH:17][CH:18]=4)[NH:13][C:12]=3[C:11]([C:26]([NH2:28])=[O:27])=[N:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.Cl[C:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[N:34]=[CH:33][N:32]=1>CC(O)C.C(OCC)(=O)C>[CH3:25][O:24][CH2:23][CH2:22][O:21][C:16]1[CH:15]=[C:14]2[C:19]([C:20]3[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:31]5[C:40]6[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=6)[N:34]=[CH:33][N:32]=5)[C:3]=4[CH3:29])=[CH:9][N:10]=[C:11]([C:26]([NH2:28])=[O:27])[C:12]=3[NH:13]2)=[CH:18][CH:17]=1

Participants

5

Reactant 2

HCID 788644-ChloroquinazolineHCID 679945404-(3-amino-2-methylphenyl)-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indole-1-carboxamide

Product 1

HCID 547665687-(2-Methoxyethoxy)-4-(2-methyl-3-(quinazolin-4-ylamino)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamideYield 25.5%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of 4-(3-amino-2-methylphenyl)-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indole-1-carboxamide (51 mg, 0.131 mmol), and 4-chloroquinazoline (47.3 mg, 0.287 mmol) in 2-Propanol (5 mL) was heated at 115° C. under microwave for 30 min. The mixture was diluted with ethyl acetate (80 mL), washed with saturated NaHCO3 solution (20 mL) and brine (20 mL), and dried over anhydrous MgSO4. The solvent was removed under vacuum, and the residue was purified by reverse phase HPLC. The correct fractions were concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (18.0 mg, 0.033 mmol, 25.5% yield) as a yellow solid. LCMS (M+H)+=519.30. 1H NMR (500 MHz, DMSO-d6) δ: 11.65 (s, 1H), 10.17 (s, 1H), 8.61 (s, 1H), 8.55 (d, J=8.0 Hz, 1H), 8.29 (s, 1H), 8.19 (s, 1H), 7.89 (m, 1H), 7.80 (d, J=8.3 Hz, 1H), 7.75 (s, 1H), 7.66 (m, 1H), 7.55-7.49 (m, 2H), 7.38-7.36 (m, 2H), 7.33 (d, J=8.9 Hz, 1H), 6.80 (dd, J1=8.7 Hz, J2=2.4 Hz, 1H), 4.17 (m, 2H), 3.73 (m, 2H), 3.34 (s, 3H), 1.87 (s, 3H).

Workup

  1. washwashed with saturated NaHCO3 solution (20 mL) and brine (20 mL)
  2. dry with materialdried over anhydrous MgSO4
  3. customThe solvent was removed under vacuum
  4. customthe residue was purified by reverse phase HPLC
  5. concentrationThe correct fractions were concentrated under vacuum
  6. extractionextracted with ethyl acetate (3×30 mL)
  7. extractionThe combined extract
  8. washwas washed with brine (30 mL)
  9. dry with materialdried over anhydrous MgSO4
  10. customRemoval of solvent under vacuum

Sources & evidence

ORD record
ord-c5b29c1bb3e84848b7ab2429d451dcaf
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

Loading…