Hydrochloric Acid → HCID 61564183, compound

HRID 1498701Notes

Reaction equation

[OH-].[Na+].Br[CH2:4][C:5]([OH:7])=[O:6].[CH3:8][C:9]1[CH:10]=[C:11]([CH:14]=[C:15]([CH3:18])[C:16]=1[OH:17])[CH:12]=[O:13].Cl>O>[CH:12]([C:11]1[CH:14]=[C:15]([CH3:18])[C:16]([O:17][CH2:4][C:5]([OH:7])=[O:6])=[C:9]([CH3:8])[CH:10]=1)=[O:13]

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of sodium hydroxide (2.53 g, 63.25 mmol) in water (65 mL) was added to a mixture of bromoacetic acid (5.27 g, 37.95 mmol) and 3,5-dimethyl-4-hydroxy-benzaldehyde (1.9 g, 12.65 mmol) in water (30 mL). The reaction mixture was stirred at 100° C. for 24 h. The solution was acidified to pH ˜2 with conc. HCl. The brown solid was filtered off, washed with water, dried under vacuum, and purified by column chromatography to give (4-formyl-2,6-dimethyl-phenoxy)-acetic acid as a light brown solid (0.40 g). To a solution of 2-amino-4,6-dimethoxybenzamide (0.150 g, 0.764 mmol) in N,N-dimethyl acetamide (5 mL) were added (4-formyl-2,6-dimethyl-phenoxy)-acetic acid (0.159 g, 0.764 mmol), sodium hydrogen sulphite (58.5%, 0.150 g, 0.84 mmol) and p-toluenesulfonic acid (15 mg, 0.0764 mmol). The reaction mixture was stirred at 150° C. for 3 h. it was then cooled to room temperature and water (40 mL) was added. A yellow precipitate was formed and filtered off, washed with water and a small amount of methanol. Triturated with 10% methanol in ether to give 0.084 g of compound, which was further purified by preparative HPLC to give 2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)acetic acid (47 mg, 13%) as a white solid. Selected data: MS (ES) m/z: 384.0; MP 270-272° C.

Workup

filtrationThe brown solid was filtered off
washwashed with water
customdried under vacuum
custompurified by column chromatography

Sources & evidence

ORD record: ord-6dd3da2ff59a4fe99f9b2607b24ebde4
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199990B2

Reaction notes

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