Water → (S)-3-[1-(4,6-dimethyl-benzo[d]isothiazol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-pyrido[3,2-d]pyrimidin-3-yl]-pentanoic acid methyl ester

HRID 1887193Notes

Reaction equation

HRID 1887193 reaction equation
[CH3:1][O:2][C:3](=[O:20])[CH2:4][C@@H:5]([N:8]1[C:13](=[O:14])[C:12]2[N:15]=[CH:16][CH:17]=[CH:18][C:11]=2[NH:10][C:9]1=[O:19])[CH2:6][CH3:7].Br[CH2:22][C:23]1[C:27]2[C:28]([CH3:33])=[CH:29][C:30]([CH3:32])=[CH:31][C:26]=2[S:25][N:24]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH3:1][O:2][C:3](=[O:20])[CH2:4][C@@H:5]([N:8]1[C:13](=[O:14])[C:12]2[N:15]=[CH:16][CH:17]=[CH:18][C:11]=2[N:10]([CH2:22][C:23]2[C:27]3[C:28]([CH3:33])=[CH:29][C:30]([CH3:32])=[CH:31][C:26]=3[S:25][N:24]=2)[C:9]1=[O:19])[CH2:6][CH3:7]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 584973913-Bromomethyl-4,6-dimethyl-benzo[d]isothiazoleHCID 67502136HCID 67502136, compound

Product 1

HCID 67503561(S)-3-[1-(4,6-dimethyl-benzo[d]isothiazol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-pyrido[3,2-d]pyrimidin-3-yl]-pentanoic acid methyl esterYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 60 mg of (S)-3-(2,4-dioxo-1,4-dihydro-2H-pyrido[3,2-d]pyrimidin-3-yl)-pentanoic acid methyl ester in N,N-dimethylformamide (2.0 mL) is added 66 mg of 3-bromomethyl-4,6-dimethyl-1,2-benzoisothiazole and 36 mg potassium carbonate at room temperature. The mixture is heated to 60° C. for 2.5 h. Then 50 mL of water is added and the product is extracted with ethyl acetate (3×50 mL). The combined organic layers are dried over sodium sulfate and concentrated. The residue is purified by flash chromatography on silica gel to give 80 mg (82%) of (S)-3-[1-(4,6-dimethyl-benzo[d]isothiazol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-pyrido[3,2-d]pyrimidin-3-yl]-pentanoic acid methyl ester.

Workup

  1. extractionthe product is extracted with ethyl acetate (3×50 mL)
  2. dry with materialThe combined organic layers are dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue is purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-81b23f3d408741b9a5dc660a0e865b4f
Source dataset
uspto-grants-2013_08
Patent number
US08501749B2

Reaction notes

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