Diisopropyl Ether → 2,2-Dimethyl-5-((thiophen-3-ylamino)methylene)-1,3-dioxane-4,6-dione

HRID 2297792Notes

Reaction equation

HRID 2297792 reaction equation
[CH3:1][C:2]1([CH3:10])[O:7][C:6](=[O:8])[CH2:5][C:4](=[O:9])[O:3]1.[CH:11](OCC)(OCC)OCC.[S:21]1[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22]1.C(OC(C)C)(C)C>>[CH3:1][C:2]1([CH3:10])[O:7][C:6](=[O:8])[C:5](=[CH:11][NH:26][C:23]2[CH:24]=[CH:25][S:21][CH:22]=2)[C:4](=[O:9])[O:3]1

Participants

5

Reactant 4

HCID 7914Diisopropyl EtherHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 31214Ethyl orthoformateHCID 640543Thiophen-3-amine

Product 1

HCID 222500872,2-Dimethyl-5-((thiophen-3-ylamino)methylene)-1,3-dioxane-4,6-dione

Conditions

Temperature
30 °C

Procedure

Dimethyl-[1,3]dioxane-4,6-dione (5.0 g, 34.6 mmol) was combined with triethyl orthoformate (205 mL, 138 mmol) and stirred at 30° C. for 1 hour. Thiophen-3-ylamine (2.81 g, 28.3 mmol) was added in small portions at room temperature, at which time a white percipitate. The mixture was heated at 85° C. overnight. The reaction mixture was cooled to room temperature and isopropyl ether was added and the suspension was stirred for one hour. The precipitate was filtered off and washed with isopropyl ether and dried in vacuo. The intermediate was dissolved in methylene chloride and potassium carbonate was added and the suspension was stirred for 30 minutes. The solid was filtered off and the solution was concentrated to give 2,2-dimethyl-5-(thiophen-3-ylaminomethylene)-[1,3]dioxane-4,6-dione as the free base. In a single neck round bottom flask, dowtherm A (15 mL) was heated to 260° C. and 2,2-dimethyl-5-(thiophen-3-ylaminomethylene)-11,3]dioxane-4,6-dione was added in small portions. The mixture heated for 30 minutes and then was cooled to room temperature and isopropyl ether was added and the suspension was stirred for one hour. The precipitate was filtered off and washed with isopropyl ether and dried in vacuo to provide 3.43g (79%) of 4H-thieno[3,2-b]pyridin-7-one. 1H NMR (400 MHz, DMSO) d 7.93 (d, 1H), 7.79 (d, 1H), 7.21 (d, 1H), 5.99 (d, 1H); LC-MS: 152 (MH+); HPLC RT: 1.21.

Workup

  1. temperatureThe mixture was heated at 85° C. overnight
  2. temperatureThe reaction mixture was cooled to room temperature
  3. stirringthe suspension was stirred for one hour
  4. filtrationThe precipitate was filtered off
  5. washwashed with isopropyl ether
  6. customdried in vacuo
  7. dissolutionThe intermediate was dissolved in methylene chloride
  8. additionpotassium carbonate was added
  9. stirringthe suspension was stirred for 30 minutes
  10. filtrationThe solid was filtered off
  11. concentrationthe solution was concentrated

Sources & evidence

ORD record
ord-725f303a1c68463882c2e2245b227fd5
Source dataset
uspto-grants-2002_12
Patent number
US06492383B1

Reaction notes

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