3-(7-(Benzyloxy)-6-methoxyquinazolin-4-yloxy)aniline → 4-(3-Aminophenoxy)-6-methoxyquinazolin-7-ol

HRID 871400Notes

Reaction equation

HRID 871400 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:19][C:20]3[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=3)[NH2:23])=[N:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:27][CH3:28])C1C=CC=CC=1.[H][H]>C(O)C.[Pd]>[NH2:23][C:22]1[CH:21]=[C:20]([CH:26]=[CH:25][CH:24]=1)[O:19][C:13]1[C:12]2[C:17](=[CH:18][C:9]([OH:8])=[C:10]([O:27][CH3:28])[CH:11]=2)[N:16]=[CH:15][N:14]=1

Participants

5

Reactant 2

HCID 668760933-(7-(Benzyloxy)-6-methoxyquinazolin-4-yloxy)anilineHCID 178418361HCID 178418361, compound

Product 1

HCID 1363377714-(3-Aminophenoxy)-6-methoxyquinazolin-7-olYield 44%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A stirred mixture of 3-(7-(benzyloxy)-6-methoxyquinazolin-4-yloxy)aniline from the previous step (2.52 g, 6.76 mmol) and palladium (10% wt on activated carbon) (200 mg) in ethanol (100 mL), under 1 atmosphere of hydrogen gas, was heated at 50° C. for 45 mins. The reaction mixture was filtered through a celite plug and concentrated under reduced pressure. The residue was purified via silica gel chromatography eluting with 1% to 10% methanol in dichloromethane to afford 4-(3-aminophenoxy)-6-methoxyquinazolin-7-ol as a colorless solid (840 mg, 44%). 1H NMR (300 MHz, DMSO-d6) δ 10.73 (brs, 1H), 8.47 (s, 1H), 7.50 (s, 1H), 7.21 (s, 1H), 7.08 (m, 1H), 6.35-6.50 (m, 3H), 5.28 (brs, 2H), 3.97 (s, 3H); LC-MS (ESI) m/z 284 (M+H)+.

Workup

  1. filtrationThe reaction mixture was filtered through a celite plug
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified via silica gel chromatography
  4. washeluting with 1% to 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-4c6ad6e16ee84994ad852c3e45b86d8f
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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