p-Toluenesulfonic acid monohydrate → 6-bromo-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one

HRID 336777

Reaction equation

HRID 336777 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[Si:12]([O:19][CH2:20][CH2:21][O:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][C:24]=1[CH3:31])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].OS([O-])=O.[Na+].[CH3:37]C1C=CC(S(O)(=O)=O)=CC=1.O>CC(N(C)C)=O.O>[Br:11][C:8]1[CH:7]=[C:3]2[C:2](=[CH:10][CH:9]=1)[N:1]=[C:27]([C:26]1[CH:25]=[C:24]([CH3:31])[C:23]([O:22][CH2:21][CH2:20][OH:19])=[C:30]([CH3:37])[CH:29]=1)[NH:6][C:4]2=[O:5].[Br:11][C:8]1[CH:7]=[C:3]2[C:2](=[CH:10][CH:9]=1)[N:1]=[C:27]([C:26]1[CH:29]=[C:30]([CH3:37])[C:23]([O:22][CH2:21][CH2:20][O:19][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[C:24]([CH3:31])[CH:25]=1)[NH:6][C:4]2=[O:5]

Participants

8

Reactant 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 50192712-Amino-5-bromobenzamideHCID 23665763Sodium BisulfiteHCID 866107984-[2-(Tert-butyl-dimethylsilanyloxy)-ethoxy]-3-methylbenzaldehyde

Product 2

HCID 1360379926-bromo-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-oneYield 22%HCID 1360380196-bromo-2-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-oneYield 10%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

A mixture of 2-amino-5-bromobenzamide (0.100 g, 0.465 mmol), 4-(2-(tert-butyldimethylsilyloxy)ethoxy)-3-methylbenzaldehyde (0.143 g, 0.465 mmol), NaHSO3 (94%, 0.0515 g, 0.465 mmol), and p-TsOH.H2O (0.00885 g, 0.0465 mmol) in DMA (5.81 mL) was heated at reflux for 15 min, cooled to room temperature, the water (20 mL) was added. The precipitate was filtered, washed with water, triturated with acetone and filtered again. The crude solid was chromatographed on silica gel (CH2Cl2/CH3OH) to provide 6-bromo-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one (0.0395 g, 22%) and 6-bromo-2-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one (0.0227 g, 10%) as white solids. Selected data for 6-bromo-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one: 1H NMR (300 MHz, DMSO-d6) δ 12.48 (s, 1H), 8.20 (d, J=2.34 Hz, 1H), 8.01-7.80 (m, 3H), 7.66 (d, J=8.72 Hz, 1H), 4.90 (t, J=5.46 Hz, 1H), 3.85 (t, J=4.87 Hz, 2H), 3.73 (dd, J=10.06, 5.11 Hz, 2H), 2.32 (s, 6H); MS (APCI) m/z 345 [M+H]+. Selected data for 6-bromo-2-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one: 1H NMR (300 MHz, DMSO-d6) δ 12.49 (s, 1H), 8.20 (d, J=2.34 Hz, 1H), 7.95 (dd, J=8.71, 2.41 Hz, 1H), 7.90 (s, 2H), 7.67 (d, J=8.72 Hz, 1H), 3.90 (m, 4H), 2.32 (s, 6H), 0.90 (s, 9H), 0.09 (s, 6H); MS (APCI) m/z 503 [M+H]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 15 min
  3. filtrationThe precipitate was filtered
  4. washwashed with water
  5. customtriturated with acetone
  6. filtrationfiltered again
  7. customThe crude solid was chromatographed on silica gel (CH2Cl2/CH3OH)

Sources & evidence

ORD record
ord-663c3dff22d54e01a4d041f0073ee261
Source dataset
uspto-grants-2014_11
Patent number
US08889698B2

Linked notes

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