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9th July 2014 @ 09:27

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 @ 02:40

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
3rd July 2014 @ 10:38

 

 

Conditions from Synthesis of 3-(7-aminothiazolo[4,5-d]pyrimidin-2-yl)-4-methyl-benzenesulfonamide (PT-22) were used on a 2x scale, to synthesise OSM-S-106.

 

PT-21-B1 (56.7 mg, 0.2 mmol) was dissolved in isopropyl alcohol (4 mL) and to this was added PT-18-D1 (68 mg, 0.24 mmol, 1.2 eq) followed by potassium carbonate solution (1M, 0.4 mL, 2 equivalents). The solution was degassed with nitrogen for 5 minutes and Pd(dppf)2.CH2Cl2 (32 mg, 40 umol, 20 mol%) was added. The reaction was heated to 90°C for 30 minutes under microwave irradiation in a sealed vessel, then evaporated to dryness. NMR (B1) indicated peaks consistent with a single major product, the title compound, plus misc. impurities (Reference spectrum):

PT-23-B1 1H NMR detail.png

The crude mixture was purified by dry flash column chromatography (gradient: 100% chloroform to 80% chloroform, 18% methanol, 2% sat. aq. ammonia) to give the title compound in two batches: 

C1, pale tan solid, 32.3 mg, 0.105 mmol, 52.8%

C2, tan solid, 23.1 mg, 0.075 mmol, 37.7%

Combined yield: 90.5%


Attached Files
2nd July 2014 @ 13:41

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 March 2014 @ 13:46

 

As per US2006199817 (page 53). p-toluenesulfonamide (4 g, 2.32 mmol) and iron (0.81 g, 250 mesh, 14.72 mmol, 6.35 equivalents) were stirred[1] and to the mixture was slowly added bromine (12 mL).[2] The reaction was stirred in air for 1 hour and then slowly poured into sodium thiosulfate (1M, 200 mL) with vigorous stirring.[3] The aqueous layer was extracted with dichloromethane (200 mL * 2) and the combined organic layers were dried over magnesium sulfate and concentrated in vacuo to give a yellow-white solid (7.41g). 1H NMR (B1) indicated 2 parts of the desired product, contaminated with 1 part starting material and no undesired regioisomers or multiply-brominated species (less than 0.2%). TLC indicated co-elution of starting material with product (dichloromethane, Rf ca. 0.3). Therefore, the reaction was repeated exactly as previously described and left stirring overnight.

After 16 hours, 1H NMR from a mini-workup (D1) indicated completion, and the reaction was diluted with dichloromethane (150 mL) and quenched by the addition of aqueous sodium thiosulfate (1M, 300 mL) with stirring. The organic layer was separated and the aqueous layer extracted with a further portion of dichloromethane (150 mL). The combined organic layers were dried over magnesium sulfate and filtered through a short plug of silica, which was then flushed with methanol/dichloromethane (1:9 v/v, 50 mL). The combined organic fractions were concentrated in vacuo to give a yellow solid containing only the desired product (by NMR) and significant insoluble impurities thought to be elemental sulfur.

 

 

Reactant: InChI=1S/C7H9NO2S/c1-6-2-4-7(5-3-6)11(8,9)10/h2-5H,1H3,(H2,8,9,10)

Product: InChI=1S/C7H8BrNO2S/c1-5-2-3-6(4-7(5)8)12(9,10)11/h2-4H,1H3,(H2,9,10,11)

 

Colloquial observations:

1) The iron sticks to the magnetic stirrer. This is fine.

2) There is a slight exotherm upon addition but temperature is effectively controlled by boil-off of bromine. 

3) The reaction flask was rinsed out with a little DCM until colourless; no trace of metallic iron remained.

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