3-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline → 1-(3-(2-Cyanopropan-2-yl)phenyl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea

HRID 631605Notes

Reaction equation

HRID 631605 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].[C:23]([C:25]([C:28]1[CH:29]=[C:30]([NH:34][C:35](=O)[O:36]C2C=CC=CC=2)[CH:31]=[CH:32][CH:33]=1)([CH3:27])[CH3:26])#[N:24]>C1COCC1.CN(C1C=CN=CC=1)C>[C:23]([C:25]([C:28]1[CH:29]=[C:30]([NH:34][C:35]([NH:19][C:18]2[CH:20]=[CH:21][CH:22]=[C:16]([O:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][N:7]=3)[CH:17]=2)=[O:36])[CH:31]=[CH:32][CH:33]=1)([CH3:27])[CH3:26])#[N:24]

Participants

5

Reactant 2

HCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 66877200Phenyl 3-(2-cyanopropan-2-yl)phenylcarbamate

Product 1

HCID 582678161-(3-(2-Cyanopropan-2-yl)phenyl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)ureaYield 20.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline (47 mg, 0.15 mmol), prepared as described in Example 113A, in THF (3 ml) was added DMAP (18 mg, 0.15 mmol) and phenyl 3-(2-cyanopropan-2-yl)phenylcarbamate (89 mg, 0.3 mmol). The reaction mixture was stirred at rt for 24 h. Concentration under reduced pressure gave a residue which was purified by preparative HPLC (Phenomenex phenylhexyl reverse phase column). The obtained solid was triturated with anhydrous diethyl ether to afford 1-(3-(2-cyanopropan-2-yl)phenyl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea (14.9 mg, 20%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 1.66 (s, 6H), 3.99 (s, 6H), 6.92 (d, J=8.7 Hz, 1H), 7.11 (d, J=7.8 Hz, 1H), 7.30-7.40 (m, 4H), 7.57-7.66 (m, 4H), 8.56 (s, 1H), 8.90 (d, J=7.5 Hz, 2H); LC-MS (ESI) m/z 484 (M+H)1

Workup

  1. concentrationConcentration under reduced pressure
  2. customgave a residue which
  3. customwas purified by preparative HPLC (Phenomenex phenylhexyl reverse phase column)
  4. customThe obtained solid was triturated with anhydrous diethyl ether

Sources & evidence

ORD record
ord-17ca6f496ddd4983bedf4fb80959c8a4
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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