Amino-thienopyrimidine Series

Postponed until tomorrow as microwave not accessible today

A solution of AEW 98-1 (29 mg, 0.12 mmol, 1 equiv.), MNR 103-  (40 mg,  0.14 mmol, 1.2 equiv.) and PdCl₂dppf (17 mg, 0.02 mmol, 0.20 equiv.) in isopropanol (2.4 mL) and K₂CO₃ (1 M, 0.24 mL, 0.22 mmol, 2.0 equiv.) was degassed with argon for 10 minutes.

The reaction mixture was heated at 90 ^oC for 30 minutes in a microwave reactor (200 W).

Hazard and Risk Assessment:

See http://malaria.ourexperiment.org/uri/3da and links within

InChi:

InChI=1S/C7H6BrN3S/c1-9-7-6-4(10-3-11-7)2-5(8)12-6/h2-3H,1H3,(H,9,10,11)

and

InChI=1S/C12H18BNO4S/c1-11(2)12(3,4)18-13(17-11)9-6-5-7-10(8-9)19(14,15)16/h5-8H,1-4H3,(H2,14,15,16)

to

InChI=1S/C13H12N4O2S2/c1-15-13-12-10(16-7-17-13)6-11(20-12)8-3-2-4-9(5-8)21(14,18)19/h2-7H,1H3,(H2,14,18,19)(H,15,16,17)

A solution of AEW 100 (25 mg, 0.11 mmol, 1 equiv.), AEW 90 (40 mg,  0.13 mmol, 1.2 equiv.) and PdCl₂dppf (16 mg, 0.02 mmol, 0.20 equiv.) in isopropanol (2.1 mL) and K₂CO₃ (1 M, 0.21 mL, 0.21 mmol, 2.0 equiv.) was degassed with argon for 10 minutes.

The reaction mixture was heated at 90^oC for 30 minutes in a microwave reactor (200 W).

Hazard and Risk Assessment:

See http://malaria.ourexperiment.org/uri/3da and links within

InChi:

InChI=1S/C6H4BrN3S/c7-4-1-3-5(11-4)6(8)10-2-9-3/h1-2H,(H2,8,9,10)

and

InChI=1S/C14H22BNO4S/c1-13(2)14(3,4)20-15(19-13)11-8-7-9-12(10-11)21(17,18)16(5)6/h7-10H,1-6H3

to

InChI=1S/C14H14N4O2S2/c1-18(2)22(19,20)10-5-3-4-9(6-10)12-7-11-13(21-12)14(15)17-8-16-11/h3-8H,1-2H3,(H2,15,16,17)

A solution of AEW 100 (26 mg, 0.11 mmol, 1 equiv.), AEW 69-1 (40 mg,  0.13 mmol, 1.2 equiv.) and PdCl₂dppf (16 mg, 0.02 mmol, 0.20 equiv.) in isopropanol (2.2 mL) and K₂CO₃ (1 M, 0.24 mL, 0.22 mmol, 2.0 equiv.) was degassed with argon for 10 minutes.

The reaction mixture was heated at 90^oC for 30 minutes in a microwave reactor (200 W).

Hazard and Risk Assessment:

See http://malaria.ourexperiment.org/uri/3da and links within

InChi:

InChI=1S/C6H4BrN3S/c7-4-1-3-5(11-4)6(8)10-2-9-3/h1-2H,(H2,8,9,10)

and

InChI=1S/C13H20BNO4S/c1-12(2)13(3,4)19-14(18-12)10-7-6-8-11(9-10)20(16,17)15-5/h6-9,15H,1-5H3

to

InChI=1S/C13H12N4O2S2/c1-15-21(18,19)9-4-2-3-8(5-9)11-6-10-12(20-11)13(14)17-7-16-10/h2-7,15H,1H3,(H2,14,16,17)

A solution of AEW 100 (23 mg, 0.1 mmol, 1 equiv.), AEW 92-1 (40 mg,  0.12 mmol, 1.2 equiv.) and PdCl₂dppf (14 mg, 0.02 mmol, 0.20 equiv.) in isopropanol (2.0 mL) and K₂CO₃ (1 M, 0.20 mL, 0.20 mmol, 2.0 equiv.) was degassed with argon for 10 minutes.

The reaction mixture was heated at 90 ^oC for 30 minutes in a microwave reactor (200 W). Reaction mixture turned from red mixture to black. The RM was diluted with MeOH (10 mL), filtered over Celite^TM, washed with MeOH (4 x 10 mL), filtered and evaporated to give a black solid.

Purification by flash column chromatography over silica:

Data:

TLC (95:4.5:0.5 CH₂Cl₂/MeOH/NH₄)

First and second elution of same plate - shows SM and product have similar Rf but reaction complete.

Hazard and Risk Assessment:

See http://malaria.ourexperiment.org/uri/3da and links within

InChi:

InChI=1S/C6H4BrN3S/c7-4-1-3-5(11-4)6(8)10-2-9-3/h1-2H,(H2,8,9,10)

and

InChI=1S/C16H24BNO4S/c1-15(2)16(3,4)22-17(21-15)13-8-7-9-14(12-13)23(19,20)18-10-5-6-11-18/h7-9,12H,5-6,10-11H2,1-4H3

to

InChI=1S/C16H16N4O2S2/c17-16-15-13(18-10-19-16)9-14(23-15)11-4-3-5-12(8-11)24(21,22)20-6-1-2-7-20/h3-5,8-10H,1-2,6-7H2,(H2,17,18,19)