4-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Amino-4-chloro-thieno[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (7.62 g, 29.57 mmol) was added to 4-Methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (7.28 g, 29.57 mmol) followed by sodium hydrogen carbonate (7.45 g, 88.71 mmol). DMF (110 mL) was added followed by water (22 mL) and the suspension was degassed by evacuation—nitrogen purge (3 cycles), followed by bubbling nitrogen gas through the stirred reaction mixture for 5 minutes. Bis(triphenylphosphine) palladium (II) chloride (500 mg, 0.739 mmol) was added and reaction mixture was heated to 85 degrees C. (oil-bath temperature) for 18 hours. Reaction mixture was allowed to cool to room temperature and DMF removed in vacuo. The residue was partitioned between ethyl acetate (500 mL) and water (400 mL) and the mixture was stirred vigorously for 15 min before being filtered through a pad of celite to remove Pd solids. Filter cake was washed with ethyl acetate (2×50 mL) and combined filtrate phases were separated and the organic phase was washed with water (1×300 mL) then saturated sodium chloride solution (250 mL). Organic phase was dried over Na2SO4 and filtered, and filtrate solvents removed in vacuo to afford a brown oily solid which was triturated with ethyl acetate to afford product as a brown solid (5.42 g, 56%) the suspension was degassed by evacuation—nitrogen purge (3 cycles) by bubbling nitrogen gas through the stirred reaction mixture for 5 minutes reaction mixture Reaction mixture to cool to room temperature DMF removed in vacuo The residue was partitioned between ethyl acetate (500 mL) and water (400 mL) before being filtered through a pad of celite to remove Pd solids Filter cake was washed with ethyl acetate (2×50 mL) were separated the organic phase was washed with water (1×300 mL) Organic phase was dried over Na2SO4 filtered filtrate solvents removed in vacuo to afford a brown oily solid which was triturated with ethyl acetate

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Amino-4-chloro-thieno[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (7.62 g, 29.57 mmol) was added to 4-Methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (7.28 g, 29.57 mmol) followed by sodium hydrogen carbonate (7.45 g, 88.71 mmol). DMF (110 mL) was added followed by water (22 mL) and the suspension was degassed by evacuation—nitrogen purge (3 cycles), followed by bubbling nitrogen gas through the stirred reaction mixture for 5 minutes. Bis(triphenylphosphine) palladium (II) chloride (500 mg, 0.739 mmol) was added and reaction mixture was heated to 85 degrees C. (oil-bath temperature) for 18 hours. Reaction mixture was allowed to cool to room temperature and DMF removed in vacuo. The residue was partitioned between ethyl acetate (500 mL) and water (400 mL) and the mixture was stirred vigorously for 15 min before being filtered through a pad of celite to remove Pd solids. Filter cake was washed with ethyl acetate (2×50 mL) and combined filtrate phases were separated and the organic phase was washed with water (1×300 mL) then saturated sodium chloride solution (250 mL). Organic phase was dried over Na2SO4 and filtered, and filtrate solvents removed in vacuo to afford a brown oily solid which was triturated with ethyl acetate to afford product as a brown solid (5.42 g, 56%) the suspension was degassed by evacuation—nitrogen purge (3 cycles) by bubbling nitrogen gas through the stirred reaction mixture for 5 minutes reaction mixture Reaction mixture to cool to room temperature DMF removed in vacuo The residue was partitioned between ethyl acetate (500 mL) and water (400 mL) before being filtered through a pad of celite to remove Pd solids Filter cake was washed with ethyl acetate (2×50 mL) were separated the organic phase was washed with water (1×300 mL) Organic phase was dried over Na2SO4 filtered filtrate solvents removed in vacuo to afford a brown oily solid which was triturated with ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4 dichloropyrimidine and 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde was coupled following procedure A. The yield was 80%. LC-MS showed the product was >95% pure and had the expected M+H+ of 233. 1H NMR (Varian 300 MHz, CDCl3, shifts relative to the solvent peak at 7.24 ppm) δ 10.0 (s, 1H) 8.7 (s, 1H) 7.9 (d, 2H) 7.5 (d, 2H), 2.5 (s, 3H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4 dichloropyrimidine and 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde was coupled following procedure A. The yield was 80%. LC-MS showed the product was >95% pure and had the expected M+H+ of 233. 1H NMR (Varian 300 MHz, CDCl3, shifts relative to the solvent peak at 7.24 ppm) δ 10.0 (s, 1H) 8.7 (s, 1H) 7.9 (d, 2H) 7.5 (d, 2H), 2.5 (s, 3H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4 dichloropyrimidine and 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde was coupled following procedure A. The yield was 80%. LC-MS showed the product was >95% pure and had the expected M+H+ of 233. 1H NMR (Varian 300 MHz, CDCl3, shifts relative to the solvent peak at 7.24 ppm) δ 10.0 (s, 1H) 8.7 (s, 1H) 7.9 (d, 2H) 7.5 (d, 2H), 2.5 (s, 3H).

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Amino-4-chloro-thieno[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (7.62 g, 29.57 mmol) was added to 4-Methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (7.28 g, 29.57 mmol) followed by sodium hydrogen carbonate (7.45 g, 88.71 mmol). DMF (110 mL) was added followed by water (22 mL) and the suspension was degassed by evacuation—nitrogen purge (3 cycles), followed by bubbling nitrogen gas through the stirred reaction mixture for 5 minutes. Bis(triphenylphosphine)palladium (II) chloride (500 mg, 0.739 mmol) was added and reaction mixture was heated to 85 degrees C. (oil-bath temperature) for 18 hours. Reaction mixture was allowed to cool to room temperature and DMF removed in vacuo. The residue was partitioned between ethyl acetate (500 mL) and water (400 mL) and the mixture was stirred vigorously for 15 min before being filtered through a pad of celite to remove Pd solids. Filter cake was washed with ethyl acetate (2×50 mL) and combined filtrate phases were separated and the organic phase was washed with water (1×300 mL) then saturated sodium chloride solution (250 mL). Organic phase was dried over Na2SO4 and filtered, and filtrate solvents removed in vacuo to afford a brown oily solid which was triturated with ethyl acetate to afford product as a brown solid (5.42 g, 56%) the suspension was degassed by evacuation—nitrogen purge (3 cycles) by bubbling nitrogen gas through the stirred reaction mixture for 5 minutes reaction mixture Reaction mixture to cool to room temperature DMF removed in vacuo The residue was partitioned between ethyl acetate (500 mL) and water (400 mL) before being filtered through a pad of celite to remove Pd solids Filter cake was washed with ethyl acetate (2×50 mL) were separated the organic phase was washed with water (1×300 mL) Organic phase was dried over Na2SO4 filtered filtrate solvents removed in vacuo to afford a brown oily solid which was triturated with ethyl acetate

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Amino-4-chloro-thieno[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (7.62 g, 29.57 mmol) was added to 4-Methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (7.28 g, 29.57 mmol) followed by sodium hydrogen carbonate (7.45 g, 88.71 mmol). DMF (110 mL) was added followed by water (22 mL) and the suspension was degassed by evacuation—nitrogen purge (3 cycles), followed by bubbling nitrogen gas through the stirred reaction mixture for 5 minutes. Bis(triphenylphosphine) palladium (II) chloride (500 mg, 0.739 mmol) was added and reaction mixture was heated to 85 degrees C. (oil-bath temperature) for 18 hours. Reaction mixture was allowed to cool to room temperature and DMF removed in vacuo. The residue was partitioned between ethyl acetate (500 mL) and water (400 mL) and the mixture was stirred vigorously for 15 min before being filtered through a pad of celite to remove Pd solids. Filter cake was washed with ethyl acetate (2×50 mL) and combined filtrate phases were separated and the organic phase was washed with water (1×300 mL) then saturated sodium chloride solution (250 mL). Organic phase was dried over Na2SO4 and filtered, and filtrate solvents removed in vacuo to afford a brown oily solid which was triturated with ethyl acetate to afford product as a brown solid (5.42 g, 56%) the suspension was degassed by evacuation—nitrogen purge (3 cycles) by bubbling nitrogen gas through the stirred reaction mixture for 5 minutes reaction mixture Reaction mixture to cool to room temperature DMF removed in vacuo The residue was partitioned between ethyl acetate (500 mL) and water (400 mL) before being filtered through a pad of celite to remove Pd solids Filter cake was washed with ethyl acetate (2×50 mL) were separated the organic phase was washed with water (1×300 mL) Organic phase was dried over Na2SO4 filtered filtrate solvents removed in vacuo to afford a brown oily solid which was triturated with ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4 dichloropyrimidine and 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde was coupled following procedure A. The yield was 80%. LC-MS showed the product was >95% pure and had the expected M+H+ of 233. 1H NMR (Varian 300 MHz, CDCl3, shifts relative to the solvent peak at 7.24 ppm) δ 10.0 (s, 1H) 8.7 (s, 1H) 7.9 (d, 2H) 7.5 (d, 2H), 2.5 (s, 3H).