Methanol → HCID 24960437, compound

HRID 336752Notes

Reaction equation

HRID 336752 reaction equation
C([O:8][CH2:9][CH2:10][O:11][C:12]1[C:17]([CH3:18])=[CH:16][C:15]([C:19]2[N:28]=[C:27](Cl)[C:26]3[C:21](=[CH:22][C:23]([O:32][CH3:33])=[CH:24][C:25]=3[O:30][CH3:31])[N:20]=2)=[CH:14][C:13]=1[CH3:34])C1C=CC=CC=1.CO.C([O-])=O.[NH4+]>C1COCC1.[Pd]>[CH3:31][O:30][C:25]1[CH:24]=[C:23]([O:32][CH3:33])[CH:22]=[C:21]2[C:26]=1[CH:27]=[N:28][C:19]([C:15]1[CH:16]=[C:17]([CH3:18])[C:12]([O:11][CH2:10][CH2:9][OH:8])=[C:13]([CH3:34])[CH:14]=1)=[N:20]2

Participants

6

Reactant 3

HCID 887MethanolHCID 2723923Ammonium formateHCID 86621920HCID 86621920, compound

Product 1

HCID 24960437HCID 24960437, compoundYield 25.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a 100 mL round bottom flask was added 2-amino-4,6-dimethoxy-benzamide (318 mg, 1.6 mmol), 4-(2-benzyloxy-ethoxy)-3,5-dimethyl-benzaldehyde (461 mg, 1.6 mmol), p-toluenesulfonic acid monohydrate (32 mg, 0.16 mmol), sodium hydrogensulfite (318 mg, 1.8 mmol) and dimethylacetamide (5 mL). The mixture was stirred in a 150° C. oil bath under nitrogen overnight. Water (40 mL) and ether (30 mL) were added. The precipitate was filtered off, washed with water then ether, and air-dried. The intermediate 2-[4-(2-benzyloxy-ethoxy)-3,5-dimethyl-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one was obtained as light brown/beige solid. Yield 474 mg (64%). 2-[4-(2-Benzyloxy-ethoxy)-3,5-dimethyl-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one (474 mg, 1.03 mmol) was stirred in phosphorus oxychloride (10 mL) at 100° C. for 4 h. Excess phosphorus oxychloride was removed under reduced pressure. Ice was added and the solid was collected. The solid was washed with water and ether, and air-dried. 2-[4-(2-benzyloxy-ethoxy)-3,5-dimethyl-phenyl]-4-chloro-5,7-dimethoxy-quinazoline was obtained as a light brown solid (yield: 356 mg, 72%). 2-[4-(2-Benzyloxy-ethoxy)-3,5-dimethyl-phenyl]-4-chloro-5,7-dimethoxy-quinazoline (192 mg, 0.4 mmol) was dissolved in a small amount of THF and 10% Pd/C (dry) (66 mg) was added. Anhydrous methanol (20 mL) and ammonium formate (955 mg) were added. The mixture was stirred in a 80° C. oil bath for 5 h. The mixture was filtered through Celite, washed with MeOH/DCM, purified by column chromatography to give 2-(4-(5,7-dimethoxyquinazolin-2-yl)-2,6-dimethylphenoxy)ethanol (36 mg, 25%) as an off-white solid. Selected data: MS (ES) m/z: 355.04; mp 169-170° C.

Workup

  1. additionwas added
  2. filtrationThe mixture was filtered through Celite
  3. washwashed with MeOH/DCM
  4. custompurified by column chromatography

Sources & evidence

ORD record
ord-36db5158330b4423a5672daafc63b656
Source dataset
uspto-grants-2014_11
Patent number
US08889698B2

Reaction notes

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