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Conclusion: Bromine substituted at both the 4- and 6- positions.
[b]Experiment start time: 9:45 am, 30/11/2012
4-Chlorothieno[3,2-d]pyrimidine (643 mg, 3.77 mmol, 1 eq) was dried and dissolved in dry THF (15 mL). This solution was stirred at -78 °C for 10 min before n-butyllithium solution (2.5 M in hexane, 1.52 mL, 3.75 mmol, 0.99 eq) was added dropwise. The solution became darker in colour. This solution was stirred at -78 °C for 30 min before elemental bromine (0.21 mL, 4.14 mmol, 1.2 equiv.) was added dropwise. Solution allowed to warm to rt. This reaction was stirred at rt for 2 hr before the reaction was quenched by the addition of water (5 mL). The reaction solution was extracted wtih chloroform (50 mL) and water (40 mL). The soluton was washed with aqueous sodium thiosulfate solution until the orange colour disappeared. The organic layer was washed with water (2 x 50 mL) and brine (30 mL) before being dried over anhydrous magnesium sulfate. The residue was concentrated in vacuo to yield an orange solid (122 mg).
Aqueous was re-extracted with EtOAc to yield a white solid (526 mg).
combined fractions were purified using flash chromatography. Three products eluted.
Fraction 1 (10% EtOAc/hexane). Looks to contain the product by 1H-NMR. 1.603 g is the recorded yield, though this weight is inaccurate. Product purified via hot filtration to yield 256.5 mg. By low res mass spec, it appears that the bromine is di-substituted at both the 4- and 6- positions.
F2(100% EtOAc): 82 mg. NOT desired product
F3 (10% MeOH/DCM): 134.5 mg. NOT desired product.
US 2006/0035908 A1
Experiment start time: 3 PM, 29/11/2012
2-Bromothiophene (0.1 mL, 1.0 mmol, 1 eq), phenylboronic acid (154 mg, 1.26 mmol, 1.26 eq), triphenylarsine (99.5 mg, 0.28 mmol, 28 mol%), K2HPO4 (605 mg, 3.47 mmol, 3.5 eq) and Pd(dba)2 (26.4 mg, 0.045 mmol, 4.5 mol%) were dissolved in a degassed sample of DME/H2O (5:1) and heated to reflux under a blanket of argon for 3 h. Reaction stopped at +3 h as per literature protocol. At +20 h ethyl acetate (50 mL) and water (50 mL) were added. The organic layer was separated, washed with water (2 x 30 mL), brine (30 mL), dried over anhydrous MgSO4 and concentrated in vacuo to yield a spotchy green paste (222 mg).
Probably contains a lot of triphenylarsine.
NEEDS TLC
IMAGE FORTHCOMING.
Experiment start time: 12:00 pm, 27/11/2012
A nicrowave reaction vessel was charged with 2-bromothiophene (0.07 mL, 0.72 mmol, 1 eq), phenylboronic acid (99.7 mg, 0.817 mmol, 1.1 eq), cesium carbonate (831 mg, 2.55 mmol, 3.5 eq) and Pd(PPh3)4 (11.5 mg, 1.25 mol %). A 30 mL solution of DME, EtOH and H2O (1:1:1) was degassed by bubbling nitrogen gas through the solution for 2 hr. 5 mL of this degassed solution was added to the microwave vessel. The contents were stirred in a microwave reactor for 15 min (150 W, 150 °C) before being allowed to cool to rt over 5 min.
TLC (hexane): visualise with UV
rf=0.9 (2-bromothiophene)
rf = 0.85 (new product)
rf=0.8 (new product)
rf=0 (phenylboronic acid)
Yield of crude product = 100.5 mg. Product was purified using a long column of silica, using hexane as the eluent. Two fractions collected:
F1: 77.2 mg
F2: 4.7 mg (garbled aromatic peaks)
Fraction was was recrystallised from benzene to yield...
HIRAC
This experiment uses slightly different conditions to those already tested in a Suzuki coupling that will hopefully generate the aminothienopyrimidine hit.
Conclusion: Thienopyrimidine series hit compound sythesised. Accurate yield not obtained. Current stock = 12.8 mg.

Experiment start time: 2pm, 26/11/2012 6-bromothieno[3,2-d]pyrimidin-4-amine (34.6 mg, 0.15 mmol, 1 eq), 3-sulfamoylphenylboronic acid, pinacol ester (46.7 mg, 0.16 mmol, 1.1 eq) and potassium acetate (59.3 mg, 0.6 mmol, 4 eq) were dissolved in 20% 1,4-dioxane/H2O and degassed for 2 hr with nitrogen gas. To the degassed solution was added PdCl2(dppf) (10 mg, 10 mol%). The resultant solution was heated at reflux for 23 hr. The solution was allowed to cool to rt. Product extracted with EtOAc (30 mL). Washed with water (2 x 20 mL), brine (20 mL), dried over MgSO4 and concentrated in vacuoto yield an orange solid. Purified via recrystallisation from 50% EtOH/H2O to yield orange crystals (12.8 mg, 0.04 mmol, 28%).*
*Yield not accurate. This number refers to current stock only.
Low res mass spec.: 634.53 ([2M+Na]+)
1H-NMR (200 MHz):
1H-NMR (300 MHz):
13C-NMR (300 MHz):

Experiment start time: 11:00 am, 26/11/2012
To thieno[3,2-d]pyrimidine-4(3H)-one (1.50 g, 9.89 mmol, 1 eq) was added phosphoryl chloride (9.21 mL, 98.9 mmol, 10 eq) dropwise, under a blanket of argon gas. The suspension was heated at reflux for 27 hr, before the solution was allowed to warm to rt. Ice was added to the solution until no effervescence was noted. Solution was then neutralised with 2.5 M sodium hydroxide solution, and saturated aqueous sodium bicarbonate solution until no effervecense was noted. Diethyl ether (100 mL) was added to the solution. The organic layer was separated, washed with water (2 x 50 mL), brine (50 mL), dried over anhydrous MgSO4 and concentrated in vacuo to yield the title product as a yellow solid, as shown by 1H-NMR spectroscopy (812 mg, 4.75 mmol, 48%).