Water → (S)-(4-Chloro-phenyl)-[1-(4,6-dimethyl-1,2-benzisothiazol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-acetic acid ethyl ester

HRID 388467Notes

Reaction equation

HRID 388467 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[C@H:5]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=1)[N:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:8][C:7]1=[O:17])[CH3:2].Br[CH2:27][C:28]1[C:32]2[C:33]([CH3:38])=[CH:34][C:35]([CH3:37])=[CH:36][C:31]=2[S:30][N:29]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:25])[C@H:5]([C:18]1[CH:19]=[CH:20][C:21]([Cl:24])=[CH:22][CH:23]=1)[N:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]([CH2:27][C:28]2[C:32]3[C:33]([CH3:38])=[CH:34][C:35]([CH3:37])=[CH:36][C:31]=3[S:30][N:29]=2)[C:7]1=[O:17])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 584973913-Bromomethyl-4,6-dimethyl-benzo[d]isothiazoleHCID 68726334(S)-(4-Chloro-phenyl)-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-acetic acid ethyl ester

Product 1

HCID 68726462(S)-(4-Chloro-phenyl)-[1-(4,6-dimethyl-1,2-benzisothiazol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-acetic acid ethyl esterYield 67%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (S)-(4-Chloro-phenyl)-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-acetic acid ethyl ester (50 mg, 0.14 mmol) (prepared according to example 1, steps 1-3) in DMF (10 mL) are added 3-Bromomethyl-4,6-dimethyl-1,2-benzisothiazole (54 mg, 0.21 mmol) (prepares according to example 5, steps 1-6) and K2CO3 (58 mg, 0.42 mmol) at room temperature under nitrogen atmosphere. The solution is heated to 100° C. for 2 hours. The solution is cooled down and water is added. The solution is extracted with EtOAc and the combined organic layer is dried with MgSO4. The solution is filtered and the filtrate is concentrated. The residue is purified by flash chromatography with 20% EtOAc in Hexane as the eluent to afford (S)-(4-Chloro-phenyl)-[1-(4,6-dimethyl-1,2-benzisothiazol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-acetic acid ethyl ester (50 mg, 67%) as a colorless foam.

Workup

  1. temperatureThe solution is cooled down
  2. extractionThe solution is extracted with EtOAc
  3. dry with materialthe combined organic layer is dried with MgSO4
  4. filtrationThe solution is filtered
  5. concentrationthe filtrate is concentrated
  6. customThe residue is purified by flash chromatography with 20% EtOAc in Hexane as the eluent

Sources & evidence

ORD record
ord-4b050abb0fd54ae6bf91800c772f86cf
Source dataset
uspto-grants-2013_02
Patent number
US08377949B2

Reaction notes

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