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

HRID 1498761Notes

Reaction equation

HRID 1498761 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: 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-20cbc63e8fbd4307a4c36863eb4ebfcd
Source dataset
uspto-grants-2015_12
Patent number
US09199990B2

Reaction notes

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