4-(Benzo[d]oxazol-5-yloxy)-3-methylbenzenamine → N-(4-(benzo[d]oxazol-5-yloxy)-3-methylphenyl)-6-(2-methoxyethoxy)quinazolin-4-amine

HRID 240580Notes

Reaction equation

HRID 240580 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH2:13][CH2:14][O:15][CH3:16])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[O:17]1[C:21]2[CH:22]=[CH:23][C:24]([O:26][C:27]3[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][C:28]=3[CH3:34])=[CH:25][C:20]=2[N:19]=[CH:18]1>C(O)(C)C.ClCCCl>[O:17]1[C:21]2[CH:22]=[CH:23][C:24]([O:26][C:27]3[CH:32]=[CH:31][C:30]([NH:33][C:2]4[C:11]5[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH2:13][CH2:14][O:15][CH3:16])[CH:10]=5)[N:5]=[CH:4][N:3]=4)=[CH:29][C:28]=3[CH3:34])=[CH:25][C:20]=2[N:19]=[CH:18]1

Participants

5

Reactant 2

HCID 669372884-(Benzo[d]oxazol-5-yloxy)-3-methylbenzenamineHCID 866508994-Chloro-6-(2-methoxyethoxy)quinazoline

Product 1

HCID 58139893N-(4-(benzo[d]oxazol-5-yloxy)-3-methylphenyl)-6-(2-methoxyethoxy)quinazolin-4-amineYield 27.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-chloro-6-(2-methoxyethoxy)quinazoline (0.199 g, 0.83 mmol) and 4-(benzo[d]oxazol-5-yloxy)-3-methylbenzenamine (0.200 g, 0.83 mmol) in isopropanol (2 mL) and DCE (2 mL). After heating to 80° C. for 12 hours, the mixture was concentrated under reduced pressure. The residue was partitioned between saturated NaHCO3 and EtOAc. The aqueous phase was extracted 2× with EtOAc, the combined organic phase was washed with brine, dried (Na2SO4), filtered and condensed. The residue was chromatographed to provide the product (0.100 g, 27%) as off-white solids. MS APCI (+) m/z 443 (M+1) detected; 1H NMR (400 MHz, DMSO-d6) δ 9.59 (s, 1H), 8.76 (s, 1H), 8.50 (s, 1H), 7.96 (s, 1H), 7.75 (m, 4H), 7.52 (dd, 1H), 7.26 (m, 1H), 7.10 (m, 1H), 6.97 (d, 1H), 4.30 (m, 2H), 3.76 (m, 2H), 3.36 (s, 3H), 2.24 (s, 3H).

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. customThe residue was partitioned between saturated NaHCO3 and EtOAc
  3. extractionThe aqueous phase was extracted 2× with EtOAc
  4. washthe combined organic phase was washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customcondensed
  8. customThe residue was chromatographed

Sources & evidence

ORD record
ord-15f14697af7c455d88840c1f46efdaee
Source dataset
uspto-grants-2014_02
Patent number
US08648087B2

Reaction notes

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