Reaction #6956

Reaction equation

3-nitrophenylguanidine

4-cyclohexyl-5-(3-dimethylamino-2-methyl-acryloyl)-2-methylsulfanyl-thiophene-3-carbonitrile

DMF-DMA

→

5-[2-(3-Nitrophenylamino)-5-methyl-pyrimidin-4-yl]-4-cyclohexyl-2-methylsulfanyl-thiophene-3-carbonitrile

Yield 42.0%

Solvents

—

hexanes

—

hexanes

EtOAc

DMF

EtOAc

toluene

Conditions

Workup

1. 1
   Otherresulting in conversion to product
2. 2
   Temperatureheated at 120° C. overnight
3. 3
   Otherresulting in conversion to product
4. 4
   OtherThe reaction was partitioned between EtOAc and water
5. 5
   Dryingthe organics were dried over sodium sulfate
6. 6
   Concentrationthen concentrated in vacuo
7. 7
   OtherThe crude product was purified by chromatography (silica gel, 10% EtOAC:hexanes)
8. 8
   Otherto afford 0.334 g (3.05 umol) of V-7 in 42% yield for 2 steps

Procedure

To a solution of 4-cyclohexyl-5-(3-dimethylamino-2-methyl-acryloyl)-2-methylsulfanyl-thiophene-3-carbonitrile (0.5 g, 1.7 mmol) in toluene (3 ml) was added DMF-DMA and the reaction was heated at 90° C. overnight resulting in conversion to product as determined by TLC (40% EtOAc:hexanes). The crude product was combined with DMF (10 ml) and 3-nitrophenylguanidine (0.5 g, 2.78 mmol) in a sealed tube and heated at 120° C. overnight resulting in conversion to product as determined by TLC (40% EtOAc:hexanes). The reaction was partitioned between EtOAc and water, the organics were dried over sodium sulfate then concentrated in vacuo. The crude product was purified by chromatography (silica gel, 10% EtOAC:hexanes) to afford 0.334 g (3.05 umol) of V-7 in 42% yield for 2 steps. 1H NMR (CDCl3) δ 1.0–2.0 (m, 10H), 2.1 (s, 3H), 2.6 (s, 3H), 7.4 (m, 1H), 7.7 (d, 1H), 7.8 (d, 1H), 8.3 (s, 1H), 8.7 (s, 1H).

Source