Dimethyl Sulfoxide → HCID 86621916, compound

HRID 555505Notes

Reaction equation

HRID 555505 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=[O:6].Br[CH2:12][CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16].C(=O)([O-])[O-].[Cs+].[Cs+].CS(C)=O>O>[C:18]([Si:15]([CH3:17])([CH3:16])[O:14][CH2:13][CH2:12][O:10][C:9]1[CH:8]=[CH:7][C:4]([CH:5]=[O:6])=[CH:3][C:2]=1[Cl:1])([CH3:21])([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 10796Cesium carbonateHCID 170223-Chloro-4-hydroxybenzaldehydeHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilane

Product 1

HCID 86621916HCID 86621916, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-chloro-4-hydroxy-benzaldehyde (227 mg, 1.45 mmol), (2-bromoethoxy)-tert-butyldimethylsilane (347 mg, 1.45 mmol), cesium carbonate (709 mg, 2.18 mmol) and DMSO (2 mL) was stirred at 80° C. for 17 h. The reaction mixture was cooled to room temperature and water (50 mL) was added. The resulting precipitate was filtered off, washed with water, air-dried, dissolved in a small amount of ethyl acetate and purified by column chromatography. 4-[2-(tert-Butyl-dimethyl-silanyloxy)-ethoxy]-3-chloro-benzaldehyde was obtained as a white solid (yield: 267 mg, 58%). To a 100 mL round-bottomed flask was added 2-amino-4,6-dimethoxy-benzamide (166 mg, 0.85 mmol), 4-[2-(tert-Butyl-dimethyl-silanyloxy)-ethoxy]-3-chloro-benzaldehyde (267 mg, 0.85 mmol), p-toluenesulfonic acid monohydrate (21 mg, 0.11 mmol), sodium hydrogensulfite (216 mg, 1.2 mmol) and dimethylacetamide (5 mL). The mixture was stirred in a 150° C. oil bath under nitrogen for 17 h. After cooling to room temperature, water (50 mL) was added. The precipitate was filtered off, washed with water and air-dried. The crude product was purified by column chromatography to give 2-(3-chloro-4-(2-hydroxyethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one (45 mg, 23%). Selected data: MS (ES) m/z: 377.03; MP 287-288° C. (decomposed).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationThe resulting precipitate was filtered off
  3. washwashed with water
  4. customair-dried
  5. dissolutiondissolved in a small amount of ethyl acetate
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-9f29e13276d242fbad7e9fadf2d7d8ab
Source dataset
uspto-grants-2011_11
Patent number
US08053440B2

Reaction notes

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