Oxalyl chloride → 3-[3-(4,6-Diethoxy-2-pyrimidinyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil

HRID 49002

Reaction equation

HRID 49002 reaction equation
[CH3:1][N:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5](=[O:12])[N:4]([C:13]2[CH:14]=[CH:15][C:16]3[S:20][N:19]=[C:18]([C:21](O)=O)[C:17]=3[CH:24]=2)[C:3]1=[O:25].C(Cl)(=O)C(Cl)=O.Cl.Cl.[C:34](=[NH:44])([O:41][CH2:42][CH3:43])[CH2:35][C:36](=[NH:40])[O:37][CH2:38][CH3:39].C(N(C(C)C)CC)(C)C>C(Cl)Cl.CN(C)C=O.C(OCC)C>[CH2:38]([O:37][C:36]1[CH:35]=[C:34]([O:41][CH2:42][CH3:43])[N:44]=[C:21]([C:18]2[C:17]3[CH:24]=[C:13]([N:4]4[C:5](=[O:12])[CH:6]=[C:7]([C:8]([F:11])([F:10])[F:9])[N:2]([CH3:1])[C:3]4=[O:25])[CH:14]=[CH:15][C:16]=3[S:20][N:19]=2)[N:40]=1)[CH3:39]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 73106Diethyl malonimidateHCID 81531DiisopropylethylamineHCID 111878605-[3,6-Dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazole-3-carboxylic acid

Product 1

HCID 206342213-[3-(4,6-Diethoxy-2-pyrimidinyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracilYield 8.31%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a cooled mixture of 5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazole-3-carboxylic acid (3.71 g, 10.0 mmol), diethyl ether and N,N-dimethylformamide (3.0 ml) is added oxalyl chloride (1.52 g, 12.0 mmol). The mixture is allowed to warm to room temperature and stirred overnight. The mixture is allowed to settle and the supernatant is decanted and concentrated in vacuo. The residue is taken up in methylene chloride and added dropwise to a stirred mixture of diethyl malonimidate dihydrochloride (2.31 g, 10.0 mmol), diisopropylethylamine (10 ml) and methylene chloride at −40° C. over one hour. The resultant mixture is allowed to warm to room temperature, diluted with methylene chloride, washed with water, 10% aqueous hydrochloric acid and water, dried over anhydrous magnesium sulfate and concentrated in vacuo to afford the title compound as a white solid (0.410 g, 8.31%, mp 197-200° C.) which is identified by NMR spectral analysis.

Workup

  1. customthe supernatant is decanted
  2. concentrationconcentrated in vacuo
  3. temperatureto warm to room temperature
  4. washwashed with water, 10% aqueous hydrochloric acid and water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-87586c6218434eba9d9754024c563445
Source dataset
uspto-grants-2004_03
Patent number
US06706663B2

Linked notes

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