Triethylamine → 2-amino-7-(4-methoxymethoxy-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester

HRID 1242060

Reaction equation

HRID 1242060 reaction equation
[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH2:14][O:13][CH:12]([CH2:17][NH2:18])[C:11]=2[S:10][C:9]=1[NH2:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][O:21][CH2:22][O:23][C:24]1[CH:32]=[CH:31][CH:30]=[C:29]2[C:25]=1[C:26](=O)[O:27][C:28]2=[O:33].Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>C(#N)C>[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH2:14][O:13][CH:12]([CH2:17][N:18]3[C:26](=[O:27])[C:25]4[C:29](=[CH:30][CH:31]=[CH:32][C:24]=4[O:23][CH2:22][O:21][CH3:20])[C:28]3=[O:33])[C:11]=2[S:10][C:9]=1[NH2:19])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219367353-Methoxymethyloxyphthalic anhydrideHCID 695860292-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester

Product 1

HCID 695859112-amino-7-(4-methoxymethoxy-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl esterYield 71.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 2-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (0.15 g, 0.53 mmol) and 4-methoxymethoxy-isobenzofuran-1,3-dione (135 mg, 0.64 mmol) was dissolved in distilled acetonitrile (7 ml) under nitrogen. The flask was cooled in an ice bath with stirring and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.12 g, 0.64 mmol), and triethylamine (0.22 ml, 1.59 mmol) were added. The reaction was warmed to ambient temperature and stirred for 18 h. The solution was concentrated in vacuo and the residue dissolved in ethyl acetate (40 ml). The organic layer was washed with 1% hydrochloric acid (2×10 ml), saturated sodium bicarbonate (10 ml), and brine (10 ml). The resulting solution was dried (Na2SO4), filtered, and the solvent evaporated in vacuo which afforded 0.18 g of a crude 2-amino-7-(4-methoxymethoxy-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester which was used without further purification.

Workup

  1. temperatureThe flask was cooled in an ice bath
  2. stirringstirred for 18 h
  3. concentrationThe solution was concentrated in vacuo
  4. dissolutionthe residue dissolved in ethyl acetate (40 ml)
  5. washThe organic layer was washed with 1% hydrochloric acid (2×10 ml), saturated sodium bicarbonate (10 ml), and brine (10 ml)
  6. dry with materialThe resulting solution was dried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvent evaporated in vacuo which

Sources & evidence

ORD record
ord-d271c70838f24f40857cc80e156283ec
Source dataset
uspto-grants-2006_10
Patent number
US07115624B1

Linked notes

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