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10th July 2014 @ 04:41

Resynthesised for hERG evaluation

AEW 100-6 (29 mg, 0.1 mmol) was dissolved in isopropyl alcohol (2 mL) and to this was added MNR 103 (34 mg, 0.12 mmol, 1.2 eq) followed by potassium carbonate solution (1M, 0.2 mL, 2 equivalents). The solution was degassed with Ar for 10 minutes and Pd(dppf)2.CH2Cl2 (16 mg, 20 umol, 20 mol%) was added and the red/pink reaction mixture was placed in the microwave reactor and heated to 85 ˚C. Originally, 200 W was applied as per optimised conditions but the temperature was unsteady. Found to be steady at 60 W and so heated to 85 ˚C at 60 W for 30 minutes. 

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/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/C12H10N4O2S2/c13-12-11-9(15-6-16-12)5-10(19-11)7-2-1-3-8(4-7)20(14,17)18/h1-6H,(H2,13,15,16)(H2,14,17,18)

Attached Files
9th July 2014 @ 08:27

Reaction scheme:

Procedure: Perfomed on 2 x 200 mg scale

AEW 99-1 (0.200 g, 0.80 mmol), isopropanol (4.5 mL) and ammonia (aq, 28% (w/w), 9 mL) were added to a sealed tube, stirred and heated at 120 °C for 2 hours. The reaction mixture was allowed to cool to room temperature and the solvent was removed under vacuum.

2 batches of CT 3 were made (total 0.400 g starting material). CT 3-6 and CT 3-7 were purified together by column chromatography over silica (99:1 DCM:MeOH to 97:3 DCM:MeOH to 96.5:3.5:0.5 DCM:MeOH:NH3).

Data:


InChI strings:

InChI=1S/C6H2BrClN2S/c7-4-1-3-5(11-4)6(8)10-2-9-3/h1-2H

to

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


9th July 2014 @ 01:40

See also AT 1-1

To MNR89-1 (1.50 g, 9.87 mmol, 1.0 equiv.) under argon was added phosphorus(V) oxychloride (15.1 g, 9.15 mL, 98.7 mmol, 10.0 equiv.) dropwise with stirring. The reaction mixture was heated to reflux and stirred for x h, before cooling to rt.

Ice (approx. 20 mL), an aqueous solution of NaHCO3 (approx. 600 mL) and solid NaHCO3 (approx. 5 g) were added sequentially until effervesence ceased and the reaction mixture was extracted with ethyl acetate (6 x 100 mL). The organic phases were combined, dried (MgSO4) and concentrated under reduced pressure to give the product as a yellow solid (xx%).  

  

HIRAC

See AT 1-1

 

InChi:

InChI=1S/C6H4N2OS/c9-6-5-4(1-2-10-5)7-3-8-6/h1-3H,(H,7,8,9)

to

InChI=1S/C6H3ClN2S/c7-6-5-4(1-2-10-5)8-3-9-6/h1-3H

Attached Files
2nd July 2014 @ 12:41

Posted in wrong place, moved to Triazolopyrazine Blog: http://malaria.ourexperiment.org/uri/647

GitHub Tag: Issue #

AEW 103-5 (500 mg, 2.48 mmol, 1 equiv.) was dissolved in DMF (3 mL) under Ar. Imidazole (220 mg, 6.18 mmol, 2.5 equiv.) was added and the reaction mixture was stirred at room temperature for 10 minutes. TBS-Cl (484 mg, 3.42 mmol, 1.3 equiv.) was then added and the reaction stirred at room temperature overnight. 

Data:

 

Hazard and Risk Assessment:

 

InChi

InChI=1S/C9H8F2O3/c1-14-9(13)8(12)5-2-3-6(10)7(11)4-5/h2-4,8,12H,1H3

to

InChI=1S/C15H22F2O3Si/c1-15(2,3)21(5,6)20-13(14(18)19-4)10-7-8-11(16)12(17)9-10/h7-9,13H,1-6H3

12th December 2013 @ 05:12

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)

Attached Files