Amino-thienopyrimidine Series

 

SM (151.9 mg), phenylboronic acid (121.9 mg), cesium fluoride (476 mg), bicarb (188 mg), dioxane (8 mL), water (2 mL) were degassed for 1 hr before Pd(PPh3)4 (50 mg) was added. Solution heated to reflux for 48 hr before being filtered through celite, and subjected to aqueous workup with DCM, water and brine to yield a light brown powder (672 mg).

TLC indicates the presence of at least 6 products.

rf=0
rf=0.4
rf=0.5
rf=0.6 (streaked)
rf=0.9 (streaked)
rf=1

HNMR is very complex. A column will be needed to purify these products.

Residue was purified via column chromatography using 10% EtOAc/petrol -> 100% EtOAc as the eluent. Two fractions were collected.

10% EtOAc/petrol: 97 mg
100% EtOAc: neg.

HNMR forthcoming

Phenylboronic acid (121.9 mg), 2-bromothiophene (0.2 mL), cesium flurode (456 mg), bicarb (187 mg), dioxane (8 mL), water (2 mL) degassed for 1 hr before Pd(PPh3)4 (50 mg) added . Heated to reflux for 48 hr. Filtered through celite, aqueous workup using DCM and water, followed by brine to yield 160 mg as a brown oil.

TLC indicates two products.

rf=0.5
rf=1

These values correspond fairly well with the starting materials (0.5=PhBoronic Acid,, 1=thiophene). Thiophene stains black with vanillin though, and the product stains blue. A column will be necessary. Residue purified using 10% EtOAc increasing in polarity to 100% EtOAc. Two products eluted showing conjugation under UV:

10% EtOAc/petrol: 128 mg
100% EtOAc: 13 mg

HNMR forthcoming

This experiment uses higher temperatures and a stronger base to protect the sulfonamide with a Boc group.

Experiment start time: 1:49 pm, 7/10/2012
147 mg SM, 291 mg Boc2O, 30 mg DMAP, 0.35 mL DIPEA, in 10 mL chloroform at reflux for 48 hr before aqueous workup in dilute acid. TLC shows nearly complete consumption of starting material, with 3 new products (though some could be either Boc2O or DMAP) at rf=1, rf=0.45, rf=0.1-0.3 (smear). Yield post workup is 119 mg. Crude NMR indicates that multiplets are present in the aromatic region that correspond to a para-substituted product, with another more complex multiplet present within. Shielded region is slightly more complex, and integration was hard, so column chromatography will be necessary.

This experiment is a Suzuki coupling between the Boc protected sulfonamide, and a thienopyrimidine unit containing no unprotected amines.

Reaction start time: 7pm, 3/10/2012
tert-butyl (3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonylcarbamate (31.5 mg, 0.082 mmol, 1 eq.), 4-chloro-6-bromothieno[3,2-d]pyrimidine (76.4 mg, 0.31 mmol, 3.8 eq.) and potassium carbonate (178.5 mg, 1.292 mmol, 15.8 eq.) were dissolved in DME (5 mL) and degassed with nitrogen for 1.5 hr. PdCl2(dppf) (10 mg, 0.013 mmol, 16 mol %) was added and the resultant suspension heated to reflux for...

crude yield = 30 mg.

Neither the aqueous nor celite, once extracted with methanol, gave products with peaks in the aromatic region of the NMR spectrum, and were thus regarded as uninteresting.

More of this material is needed. This is essentially a repeat of JRC 29-3.

Experiment start time: 11 am, 3/10/2012
3-bromobenzenesulfonamide (590.3 mg, 2.500 mmol, 1 equiv.), dried potassium acetate (911.7 mg, 9.288 mmol, 3.7 eq.) and bis(pinacolatodiborane) (1.2136 g, 4.779 mmol, 1.9 eq.) were dissolved in 1,4-dioxane (25 mL). The resultant suspension was degassed with nitrogen for 1.5 hr before PdCl2(dppf) (20 mg, 0.027 mmol, 1 mol %) was added. The resultant suspension was heated to reflux for 24 hr. Ethyl acetate (100 mL) and water (30 mL) were added to the solution, which was sonicated to promote dissolution before the solution was filtered through a pad of celite. The celite was washed with ethyl acetate (2 x 30 mL). The organic layer was separated, washed with brine (40 mL), dried over anhydrous magnesium sulfate and concentrated in vacuo to yield an alternating brown/white solid (1.361 g). The residue was purified using column chromatography (40% - 100% EtOAc/petrol), and recrystallised from 50% EtOH/H2O to yield brilliant gold flakes (434.5 mg).