p-Toluenesulfonic acid monohydrate → HCID 136038015, compound

HRID 555507Notes

Reaction equation

HRID 555507 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].C([Si](C)(C)[O:20][CH2:21][CH2:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([CH:28]=O)=[CH:26][C:25]=1[O:32][CH3:33])(C)(C)C.S([O-])(O)=O.[Na+].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[OH:20][CH2:21][CH2:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][C:9]([O:11][CH3:12])=[CH:8][C:7]=3[O:13][CH3:14])[N:1]=2)=[CH:26][C:25]=1[O:32][CH3:33]

Participants

6

Reactant 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 86621917HCID 86621917, compound

Product 1

HCID 136038015HCID 136038015, compoundYield 7.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

NaH (0.12 g, 0.0050 mol, 60% in mineral oil) was added to 4-hydroxy-3-methoxylbenzalde (0.636 g, 4.18 mmol) in anhydrous DMF (15 mL) and then (2-bromoethoxy)-tert-butyl-dimethylsilane (1.0 g, 4.18 mmol) was added and the reaction was kept at room temperature overnight. The reaction mixture was poured into water. The mixture was extracted with dichloromethane and the combined organic layers were passed through a column to yield 4-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3-methoxybenzaldehyde (170 mg, 13%). 2-Amino-4,6-dimethoxy-benzamide (101 mg, 0.515 mmol), 4-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3-methoxybenzaldehyde (160 mg, 0.515 mmol), sodium hydrogen sulfite (100 mg, 58.5%) and p-toluenesulfonic acid monohydrate (10 mg) were mixed with N,N-dimethyl acetamide (15 mL) and heated to 150° C. for 16 h. N,N-dimethyl acetamide was removed under vacuum and the residue was poured into water (50 mL). The solid was filtered off and further purified by column chromatography to yield 2-(4-(2-hydroxyethoxy)-3-methoxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one (15 mg, 7.8%). Selected data: MS (ES) m/z: 373.1; MP 246-248° C.

Workup

  1. customN,N-dimethyl acetamide was removed under vacuum
  2. additionthe residue was poured into water (50 mL)
  3. filtrationThe solid was filtered off
  4. customfurther purified by column chromatography

Sources & evidence

ORD record
ord-42c99c908b4345e999b0e4442233dc9b
Source dataset
uspto-grants-2011_11
Patent number
US08053440B2

Reaction notes

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