Valinol → 5-[3,6-Dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-N-[1-(hydroxymethyl)-2-methylpropyl]-1,2-benzisothiazole-3-carboxamide

HRID 48985

Reaction equation

HRID 48985 reaction equation
[NH2:1][CH:2]([CH:5]([CH3:7])[CH3:6])[CH2:3][OH:4].[CH3:8][N:9]1[C:14]([C:15]([F:18])([F:17])[F:16])=[CH:13][C:12](=[O:19])[N:11]([C:20]2[CH:21]=[CH:22][C:23]3[S:27][N:26]=[C:25]([C:28](Cl)=[O:29])[C:24]=3[CH:31]=2)[C:10]1=[O:32]>O1CCCC1.C(OCC)C>[CH3:8][N:9]1[C:14]([C:15]([F:18])([F:17])[F:16])=[CH:13][C:12](=[O:19])[N:11]([C:20]2[CH:21]=[CH:22][C:23]3[S:27][N:26]=[C:25]([C:28]([NH:1][CH:2]([CH2:3][OH:4])[CH:5]([CH3:7])[CH3:6])=[O:29])[C:24]=3[CH:31]=2)[C:10]1=[O:32]

Participants

5

Reactant 2

HCID 79019ValinolHCID 113038335-[3,6-Dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazole-3-carboxylic acid chloride

Product 1

HCID 206342735-[3,6-Dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-N-[1-(hydroxymethyl)-2-methylpropyl]-1,2-benzisothiazole-3-carboxamideYield 86.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-amino-3-methyl-1-butanol (1.39 g, 13.5 mmol) in anhydrous tetrahydrofuran at 0° C. is added dropwise a solution of 5-[3,6-Dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazole-3-carboxylic acid chloride (2.10 g, 5.39 mmol) in tetrahydrofuran. The resultant mixture is stirred 7.5 hours at ambient temperature, diluted with diethyl ether, washed with 1M aqueous hydrochloric acid, saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue is chromatographed on silica gel with hexanes-ethyl acetate to afford the title compound as a solid (2.12 g, 86.2%, mp 120° C.) which is identified by NMR spectral analysis.

Workup

  1. washwashed with 1M aqueous hydrochloric acid, saturated sodium bicarbonate and brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue is chromatographed on silica gel with hexanes-ethyl acetate

Sources & evidence

ORD record
ord-76a77cb533724934a7a7dde2e7182af6
Source dataset
uspto-grants-2004_03
Patent number
US06706663B2

Linked notes

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