3-Bromo-1-propanol → HCID 18327323, compound

HRID 1250225Notes

Reaction equation

HRID 1250225 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:24]=[CH:23][C:7]([O:8][CH2:9][C:10]2[NH:19][C:18](=[O:20])[C:17]3[C:12](=[C:13]([O:21][CH3:22])[CH:14]=[CH:15][CH:16]=3)[N:11]=2)=[CH:6][CH:5]=1.Br[CH2:26][CH2:27][CH2:28][OH:29]>CN(C=O)C.CCOC(C)=O>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([O:8][CH2:9][C:10]2[N:19]([CH2:26][CH2:27][CH2:28][OH:29])[C:18](=[O:20])[C:17]3[C:12](=[C:13]([O:21][CH3:22])[CH:14]=[CH:15][CH:16]=3)[N:11]=2)=[CH:23][CH:24]=1

Participants

6

Reactant 3

HCID 123083-Bromo-1-propanolHCID 24758Sodium hydrideHCID 135506589HCID 135506589, compound

Product 1

HCID 18327323HCID 18327323, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Sodium hydride (239 mg, 9.94 mmol) was added to a solution of 2-(4-chlorophenoxymethyl)-8-methoxy-3H-quinazolin-4-one (3000 mg, 9.47 mmol) in DMF (20 mL) at room temeprature. The reaction mixture was stirred for 30 min, then 3-bromopropanol (1448 mg, 0.94 mL, 10.42 mmol) was added. The reaction mixture was heated at 80° C. for 17 h, cooled to room temperature and diluted with EtOAc. The organic solution was washed with water, sat'd aq NaCl, dried and concentrated. The crude residue was purified using SiO2-gel chromatography (50% EtOAc/hexanes) to give 1.1 g of the desired N-alkylated product. API-MS: 375 (M+1). 1H NMR (300 MHz, CDCl3): d 7.82 (d, 1 H), 7.4 (t, 1 H), 7.2 (m, 3 H), 7.9 (d, 2 H), 5.2 (s, 2 H), 4.36 (t, 2 H), 4.0 (s, 3 H), 3.58 (t, 2 H), 2.0 (t, 2 H).

Workup

  1. temperaturecooled to room temperature
  2. washThe organic solution was washed with water
  3. customdried
  4. concentrationconcentrated
  5. customThe crude residue was purified
  6. customto give 1.1 g of the desired N-alkylated product

Sources & evidence

ORD record
ord-2d97240431f34c7e9e0b0dc550406fc6
Source dataset
uspto-grants-2002_01
Patent number
US06337332B1

Reaction notes

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