Carbonic acid-guanidine (1:1) → 8-Isopropyl-7-methoxy-quinazolin-2-ylamine

HRID 1609795Notes

Reaction equation

HRID 1609795 reaction equation
O[CH:2]=[C:3]1[C:8](=O)[C:7]([CH:10]([CH3:12])[CH3:11])=[C:6]([O:13][CH3:14])[CH2:5][CH2:4]1.C(=O)(O)O.[NH2:19][C:20]([NH2:22])=[NH:21]>CN(C=O)C>[CH:10]([C:7]1[C:6]([O:13][CH3:14])=[CH:5][CH:4]=[C:3]2[C:8]=1[N:21]=[C:20]([NH2:22])[N:19]=[CH:2]2)([CH3:12])[CH3:11]

Participants

4

Reactant 2

HCID 286947Carbonic acid-guanidine (1:1)HCID 696592786-Hydroxymethylene-2-isopropyl-3-methoxy-cyclohex-2-enone

Product 1

HCID 117360878-Isopropyl-7-methoxy-quinazolin-2-ylamine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 6-hydroxymethylene-2-isopropyl-3-methoxy-cyclohex-2-enone (3.5 g) and guanidine carbonate (7 g) in DMF (40 mL) was heated at 150° C. for 4 hours. The solvent was removed under reduced pressure, then ice-cold water was added to the residue. The product was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, then brine, and dried over anhydrous sodium sulfate. Solvent was removed under reduced pressure to give a crude mixture of dihydroquinazolines (4 g). The dihydroquinazolines were aromatized to the title compound by heating in nitrobenzene (70 mL) at 150° C. in the presence of 10% Pd-C (400 mg) for 3 days. The catalyst was removed by filtration, then the filtrate was concentrated, and the resulting product was purified on a column of silica gel (Hex:EtOAc) to give the title compound as an off-white solid (2.1 g, 54.2%). mp 112–113° C.; 1H NMR (CDCl3): δ 1.38 (d, 6H, 2×CH3), 3.95 (s, 3H, OCH3), 4.24 (m, 1H, CH), 5.0 (br s, 2H, NH2), 7.02 (d, 1H, Ar-H, J=9 Hz), 7.55 (d, 1H, Ar-H, J=9 Hz), 8.87 (s, 1H, Ar-H); MS m/z 218.05, C12H15N3O (M++1).

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionice-cold water was added to the residue
  3. extractionThe product was extracted with ethyl acetate (3×50 mL)
  4. washThe combined organic layers were washed with water
  5. dry with materialbrine, and dried over anhydrous sodium sulfate
  6. customSolvent was removed under reduced pressure
  7. customto give a crude

Sources & evidence

ORD record
ord-f01d5f1b57e94b2bb93372f904cc481d
Source dataset
uspto-grants-2006_01
Patent number
US06982260B1

Reaction notes

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