Ethyl ketone → 1,2,2-triethyl-6-(pyridin-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

HRID 2363961Notes

Reaction equation

HRID 2363961 reaction equation
[CH2:1]([NH:3][C:4]1[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[S:6][C:5]=1[C:15]([NH2:17])=[O:16])[CH3:2].[CH3:18][CH2:19][C:20](=O)[CH2:21][CH3:22].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+]>C(O)(=O)C>[CH2:1]([N:3]1[C:4]2[CH:8]=[C:7]([C:9]3[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=3)[S:6][C:5]=2[C:15](=[O:16])[NH:17][C:20]1([CH2:21][CH3:22])[CH2:19][CH3:18])[CH3:2]

Participants

6

Reactant 4

HCID 7288Ethyl ketoneHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 667438263-(Ethylamino)-5-(pyridin-4-yl)thiophene-2-carboxamide

Product 1

HCID 667438271,2,2-triethyl-6-(pyridin-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-oneYield 12%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-(ethylamino)-5-(pyridin-4-yl)thiophene-2-carboxamide (0.100 g, 0.400 mmol), 3-pentanone (3.0 mL), p-toluenesulfonic acid monohydrate (0.0095 g, 0.050 mmol) and acetic acid (3.0 mL) was stirred for 1 h at 120° C. in a sealed tube. Then, this mixture was stirred for 2 h at 150° C. and stirring was continued for 2 days at 110° C. in a sealed tube. The mixture was poured into sat. aqueous sodium hydrogen carbonate (150 mL). Extraction with ethyl acetate (100 mL), drying over magnesium sulfate, filtration and concentration at reduced pressure gave an oil. This oil was purified by column chromatography (Combiflash, 40 g silica gel, dichloromethane to ethyl acetate), then recrystallized from ethyl acetate, and the precipitate was collected by filtration to afford the title compound (0.0194 g, 12%) as a yellow solid:

Workup

  1. stirringThen, this mixture was stirred for 2 h at 150° C.
  2. stirringstirring
  3. waitwas continued for 2 days at 110° C. in a sealed tube
  4. extractionExtraction with ethyl acetate (100 mL)
  5. dry with materialdrying over magnesium sulfate, filtration and concentration at reduced pressure
  6. customgave an oil
  7. customThis oil was purified by column chromatography (Combiflash, 40 g silica gel, dichloromethane to ethyl acetate)
  8. customrecrystallized from ethyl acetate
  9. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-535587962d3149e285681347363d80fa
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

Loading…