p-Toluenesulfonic acid → 8-(Benzyloxy)-2-(3-(4-isopropylpiperazin-1-yl)phenyl)-5-methoxyquinazolin-4(3H)-one

HRID 922403Notes

Reaction equation

HRID 922403 reaction equation
[NH2:1][C:2]1[C:10]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][CH:8]=[C:7]([O:19][CH3:20])[C:3]=1[C:4]([NH2:6])=[O:5].[CH:21]([N:24]1[CH2:29][CH2:28][N:27]([C:30]2[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=2)[CH:33]=O)[CH2:26][CH2:25]1)([CH3:23])[CH3:22].CC1C=CC(S(O)(=O)=O)=CC=1.OS([O-])=O.[Na+]>CN(C)C(=O)C>[CH2:12]([O:11][C:10]1[CH:9]=[CH:8][C:7]([O:19][CH3:20])=[C:3]2[C:2]=1[N:1]=[C:33]([C:32]1[CH:35]=[CH:36][CH:37]=[C:30]([N:27]3[CH2:26][CH2:25][N:24]([CH:21]([CH3:23])[CH3:22])[CH2:29][CH2:28]3)[CH:31]=1)[NH:6][C:4]2=[O:5])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 23665763Sodium BisulfiteHCID 840175373-(4-Isopropylpiperazin-1-yl)benzaldehydeHCID 867193602-Amino-3-(benzyloxy)-6-methoxybenzamide

Product 1

HCID 1362488718-(Benzyloxy)-2-(3-(4-isopropylpiperazin-1-yl)phenyl)-5-methoxyquinazolin-4(3H)-oneYield 22.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 2-amino-3-(benzyloxy)-6-methoxybenzamide (11, 0.267 g, 0.98 mmol) and 5-(benzyloxy)-2-methoxybenzaldehyde (3, 0.152 g, 0.65 mmol) in N,N-dimethylacetamide (10 mL) was treated with p-TsOH (0.30 g, 1.57 mmol) and NaHSO3 (0.204 g, 1.96 mmol) and then heated at 110° C. for 15 h. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-100% 95:4.5:0.5 CH2Cl2/MeOH/concentrated NH4OH in CH2Cl2 to afford the title compound (71 mg, 22%) as a light yellow solid: 1H NMR (500 MHz, DMSO-d6) δ 12.22 (s, 1H), 7.79 (s, 1H), 7.68 (d, J=7.6 Hz, 1H), 7.56 (d, J=7.3 Hz, 2H), 7.42-7.33 (m, 5H), 7.14 (d, J=7.6 Hz, 1H), 6.92 (d, J=9.0 Hz, 1H), 5.24 (s, 2H), 3.83 (s, 3H), 3.34-3.31 (m, 4H), 2.80-2.60 (m, 5H), 1.05 (br s, 6H); ESI MS m/z 485 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by silica gel chromatography
  4. washeluting with 0-100% 95:4.5:0.5 CH2Cl2/MeOH/concentrated NH4OH in CH2Cl2

Sources & evidence

ORD record
ord-21c9af4972294b29ac22f39538e1a225
Source dataset
uspto-grants-2016_03
Patent number
US09278940B2

Reaction notes

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