4-(Piperidin-4-ylamino)benzoic Acid tert-Butyl Ester → 4-[1-(6,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl) piperidin-4-ylamino]benzoic acid tert-butyl ester

HRID 1274134Notes

Reaction equation

HRID 1274134 reaction equation
[C:1]([O:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].Cl[C:22]1[N:31]=[C:30]([O:32]C)[C:29]2[C:24](=[CH:25][C:26]([O:36][CH3:37])=[C:27]([O:34][CH3:35])[CH:28]=2)[N:23]=1>C(O)CCCC>[C:1]([O:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]2[CH2:19][CH2:18][N:17]([C:22]3[NH:31][C:30](=[O:32])[C:29]4[C:24](=[CH:25][C:26]([O:36][CH3:37])=[C:27]([O:34][CH3:35])[CH:28]=4)[N:23]=3)[CH2:16][CH2:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 106362074-(Piperidin-4-ylamino)benzoic Acid tert-Butyl EsterHCID 221203552-Chloro-4,6,7-trimethoxyquinazoline

Product 1

HCID 1355281174-[1-(6,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl) piperidin-4-ylamino]benzoic acid tert-butyl esterYield 32%

Reagents, catalysts & solvents 1

HCID 62761-PentanolSolvent

Conditions

Temperature
120 °C

Procedure

4-(Piperidin-4-ylamino)benzoic Acid tert-Butyl Ester (49) (0.47 mmol) was added to a solution of 2-chloro-4,6,7-trimethoxy-quinazoline (0.1 g, 0.39 mmol) in n-pentanol (5 mL) at 25° C. The mixture was stirred at 120° C. for 12 h. The reaction mixture was then cooled to room temperature and the desired product was filtered and rinsed with acetone to give 0.06 g (32%) of (15): TLC (Rf =0.30; 5% CH3OH/CH2Cl2); 1H NMR (DMSO) δ 11.24 (s, 1H), 7.61 (d, 2H, J=8.4), 7.26 (s, 1H), 6.76 (s, 1H), 6.60 (d, 2H, J=8.7), 6.36 (d, 1H, J=7.8), 4.24 (d, 2H, J=13.6), 3.83 (s, 3H), 3.78 (s, 3H), 3.60 (m, 1H), 3.09 (m, 2H), 1.94 (d, 2H, J=10.4), 1.48 (s, 9H), 1.40 (m, 2H) 13C NMR (DMSO) δ 165.2, 162.4, 154.9, 151.4, 150.1, 146.7, 145.6, 130.9, 117.6, 111.2, 109.2, 106.0, 105.3, 78.9, 55.7, 55.5, 48.4, 43.9, 30.9, 28.0; HRMS (FAB) m/z 481.2444 (M+H)+ (C26H32N4O5 requires 481.2443); Anal. (C26H32N4O5 ·1/2HCl) C, H, N.

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. filtrationthe desired product was filtered
  3. washrinsed with acetone

Sources & evidence

ORD record
ord-593df3d857594e7899aceefa9d73526a
Source dataset
uspto-grants-2000_12
Patent number
US06156758

Reaction notes

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