p-Toluenesulfonic acid monohydrate → ethyl (8-methyl-1,1-dioxido-4H-[1,3]oxazolo[5,4-h][1,2,4]benzothiadiazin-3-yl)acetate

HRID 601338Notes

Reaction equation

HRID 601338 reaction equation
[NH2:1][C:2]1[C:11]2[S:10](=[O:13])(=[O:12])[N:9]=[C:8]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[NH:7][C:6]=2[CH:5]=[CH:4][C:3]=1[OH:20].[CH3:21][C:22](C)(C)C([O-])([O-])[O-].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C=O>[CH3:21][C:22]1[O:20][C:3]2[CH:4]=[CH:5][C:6]3[NH:7][C:8]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:9][S:10](=[O:13])(=[O:12])[C:11]=3[C:2]=2[N:1]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 21927715TrimethylorthoacetateHCID 86594014ethyl (8-amino-7-hydroxy-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)acetate

Product 1

HCID 86594016ethyl (8-methyl-1,1-dioxido-4H-[1,3]oxazolo[5,4-h][1,2,4]benzothiadiazin-3-yl)acetateYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of the product of Example 352E (56.3 mg, 0.188 mmol) in anhydrous N,N-dimethylformamide (2 mL) was treated with trimethylorthoacetate (0.098 mL, 0.752 mmol) and p-toluenesulfonic acid monohydrate (1Mg) at room temperature for 3 hours under a nitrogen atmosphere. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel eluting with 4% methanol/dichloromethane to give the title compound as a white crystalline solid (48 mg, 79%). MS (ESI−) m/z 322 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ 1.22 (t, J=7.17 Hz, 3 H) 2.69 (s, 3 H) 3.71 (s, 2 H) 4.17 (q, J=7.11 Hz, 2 H) 7.27 (d, J=8.82 Hz, 1 H) 8.02 (d, J=8.82 Hz, 1 H) 12.33 (s, 1 H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue purified by column chromatography on silica gel eluting with 4% methanol/dichloromethane

Sources & evidence

ORD record
ord-af17865c740a482f895a1107b9e672b4
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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