Trifluoroacetic acid → HCID 178486907, compound

HRID 1295741Notes

Reaction equation

HRID 1295741 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=O.[CH3:8][NH:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.Cl[C:18]1[NH:19][C:20]2[C:25]([C:26](=[O:28])[N:27]=1)=[C:24]([O:29][CH3:30])[C:23]([O:31][CH3:32])=[C:22]([O:33][CH3:34])[CH:21]=2.[CH:35]([N:38](C(C)C)CC)(C)[CH3:36].[K+].[Br-]>C(Cl)Cl.CO.C(Cl)Cl.CCO>[CH3:30][O:29][C:24]1[C:23]([O:31][CH3:32])=[C:22]([O:33][CH3:34])[CH:21]=[C:20]2[C:25]=1[C:26](=[O:28])[N:27]=[C:18]([N:9]([CH3:8])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N:38]3[CH2:35][CH2:36][CH2:2][C:3]3=[O:5])[CH:12]=1)[NH:19]2

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7669N-MethylbenzylamineHCID 81531DiisopropylethylamineHCID 253877Potassium BromideHCID 1784868982-chloro-5,6,7-trimethoxy-1H-quinazolin-4-one

Product 1

HCID 178486907HCID 178486907, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
110 °C

Procedure

Trifluoroacetic acid (375 μL, 4.87 mmol) was added via syringe to a stirred solution of (3) from Step 2 (189 mg, 0.62 mmol) at 0° C. After 3 hours, the solution was concentrated under reduced pressure, then pumped under vacuum for 1 hour. The crude residue was dissolved in EtOH (2 mL), and added to a sealed tube containing 2-chloro-5,6,7-trimethoxy-1H-quinazolin-4-one (132 mg, 0.49 mmol), diisopropylethylamine (425 μL, 2.44 mmol), and EtOH (3 mL). The suspension was heated at 110° C. for 2 hours, then cooled to room temperature and stirred overnight. The reaction mixture was concentrated under reduced pressure, and purified by chromatography to give 128 mg (60%) of the above Example H-1 as a cream colored solid. mp 165.5–166.5° C.; TLC Rf 0.5 (5% MeOH/DCM); IR (KBr) νmax 3429, 2933, 1657, 1592, 1481, 1452, 1120, 1047, 933; 1H NMR (DMSO-d6, 2.49) 2.04 (m, 2H), 2.50 (t, 2H, J=1.9), 3.03 (s, 3H), 3.70 (s, 3H), 3.77 (s, 1H), 3.81 (t, 2H, J=6.9), 3.84 (s, 3H), 4.81 (s, 2H), 6.57 (s, 2H), 6.99 (d, 1H, J=7.7), 7.32 (t, 1H, J=7.8), 7.49 (dd, 1H, J=2.1, 7.4), 7.65 (s, 1H), 10.83 (s, 1H); MS (ES+) m/z 439 (M+H); Anal. (C23H26N4O5 w/0.25M CH2Cl2): calcd 60.75; found: 60.65; H: calcd, 5.81; found: 5.79; N: calcd, 12.19; found, 11.98).

Workup

  1. concentrationthe solution was concentrated under reduced pressure
  2. waitpumped under vacuum for 1 hour
  3. dissolutionThe crude residue was dissolved in EtOH (2 mL)
  4. additionadded to a sealed tube
  5. temperaturecooled to room temperature
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. custompurified by chromatography
  8. customto give 128 mg (60%) of the above Example H-1 as a cream

Sources & evidence

ORD record
ord-1f11c378a00d4fefacfd50b6f1a1905d
Source dataset
uspto-grants-2007_07
Patent number
US07244738B2

Reaction notes

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