Triethylamine → (7-Methoxymethoxymethyl-1,1-dioxo-1,4-dihydro-1lambda6-thieno[2,3-e][1,2,4]thiadiazin-3-yl)-acetic acid ethyl ester

HRID 1516023Notes

Reaction equation

HRID 1516023 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:11][O:12][CH2:13][O:14][CH3:15])[C:6]=1[S:7]([NH2:10])(=[O:9])=[O:8].[CH2:16]([O:18][C:19](=[O:28])[CH:20]=[C:21](OCC)OCC)[CH3:17].C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[CH2:16]([O:18][C:19](=[O:28])[CH2:20][C:21]1[NH:1][C:2]2[S:3][CH:4]=[C:5]([CH2:11][O:12][CH2:13][O:14][CH3:15])[C:6]=2[S:7](=[O:8])(=[O:9])[N:10]=1)[CH3:17]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 1693882-Propenoic acid, 3,3-diethoxy-, ethyl esterHCID 574551872-Amino-4-[(methoxymethoxy)methyl]-3-thiophenesulfonamide

Product 1

HCID 58000246(7-Methoxymethoxymethyl-1,1-dioxo-1,4-dihydro-1lambda6-thieno[2,3-e][1,2,4]thiadiazin-3-yl)-acetic acid ethyl esterYield 52.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2-amino-4-methoxymethoxymethyl-thiophene-3-sulfonic acid amide (0.76 g, 3.01 mmol) in N,N-dimethylformamide (10 mL) at 25° C. was added 3,3-diethoxy-acrylic acid ethyl ester (0.68 g, 3.61 mmol). The reaction was stirred at 70° C. for 5 h before triethylamine (1.68 mL, 12.04 mmol) was added to the mixture. The reaction was stirred at 70° C. overnight. It was then cooled to 25° C., diluted with ethyl acetate (10 mL) and washed with 1.0 M aqueous hydrochloric acid solution (10 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified via flash column chromatography (Teledyne Isco RediSep column; 0-80% ethyl acetate in hexanes) to afford the desired product, (7-methoxymethoxymethyl-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-3-yl)-acetic acid ethyl ester (0.55 g, 1.57 mmol, 52%), as a brown oil. 1H NMR (400 MHz, CDCl3) δ: 1.32 (3H, t, J=7.2 Hz), 3.42 (3H, s), 3.68 (2H, s), 4.26 (2H, q, J=7.2 Hz), 4.76 (2H, s), 4.80 (2H, s), 7.00 (1H, s), 8.00 (1H, s).

Workup

  1. additionwas added to the mixture
  2. temperatureIt was then cooled to 25° C.
  3. washwashed with 1.0 M aqueous hydrochloric acid solution (10 mL)
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via flash column chromatography (Teledyne Isco RediSep column; 0-80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-59d7e4c048c14044be1f0b846c77ca33
Source dataset
uspto-grants-2012_07
Patent number
US08222404B2

Reaction notes

Loading…