All Notebooks | Help | Support | About
23rd January 2014 @ 11:46

Yield of 45%, though solvent (mainly IPA, NH3) leaked through seal. 

Repeat of CT 3-1 with a shorter time to see if there is a difference in yield/mixture of products. 4 hours was sufficient for all starting material to disappear, but a mix of products was obtained in CT 3-1. 

Reaction scheme

Procedure

AEW 99-1 (0.100 g, 0.4 mmol), isopropanol (3 mL) and ammonia (6 mL) were added to a sealed tube, stirred and heated at 120 °C for 2 hours. The reaction mixture was cooled to rt and the solvent removed under vacuum. The crude product was purified by flash column chromatography over silica (95:4.5:0.5 DCM:MeOH:NH3) to yield the product as a yellow solid (41 mg, 0.18 mmol, 45%).

Note: Over half of the solvent had evaporated after 2 hours. Seal was not in great condition before the reaction (but worked for the last reaction), and seemed to be cracked upon inspection afterwards. 

Data

-NMR

1H NMR of crude product. Two products, the major product consistent with the desired product (CT 3-1. The other product could be the -OH substituted product (also replacing -Cl), as the reaction was concentrated in water due to a faulty seal. 

CT 3-2 crude proton.pdf

1H NMR of 3rd fraction. Chemical shifts correspond with the other major product (not the desired product), thought to possibly be the -OH substituted product (~18 mg). The fraction appears to be quite pure, so will further characterise the product to determine structure. 

CT 3-2 fraction 3 proton.pdf

1H NMR of 4th fraction. Chemical shifts correspond to the desired product (see previous CT 3-1) though with a small impurity. The fractions may require further drying, although the impurity is not a water signal. 

CT 3-2 fraction 4 proton.pdf

-TLC

Crude TLC showed two spots, consistent with two products in the 1H spectrum. 

After column chromatography

The 'smear' in tubes 9-11 appears to be 2 spots, as separated in 12-13.

4 fractions collected, co-spotted with pure product from CT 3-1

 

HIRAC

CT 3-1 HIRAC.pdf

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)

Attached Files
CT 3-1 HIRAC.pdf
CT 3-1 scheme.cdx
CT 3-1 scheme.png
CT 3-2 crude proton.pdf
CT 3-2 crude.zip
CT 3-2 fraction 3 proton.pdf
CT 3-2 fraction 4 proton.pdf
CT 3-2 fraction 3.zip
CT 3-2 fraction 4.zip
CT 3-2 column 1.JPG
CT 3-2 column 2.JPG
CT 3-2 column 3.JPG
CT 3-2 reference co-spot.JPG
Comments
Re: Synthesis of 6-Bromothieno[3,2-d]pyrimidin-4-amine (CT 3-2) by Matthew Todd
27th January 2014 @ 09:55
At the time of writing your reason for this experiment is "Repeat of CT 3-1 with a shorter time to see if there is a difference in yield." - what was the yield of 3-1 and why do you think shorter rxn time is the solution? Did you think that you had product decomposition?
Re: Synthesis of 6-Bromothieno[3,2-d]pyrimidin-4-amine (CT 3-2) by Carmen Tran
28th January 2014 @ 03:43
Info has been updated in the relevant posts, but yield of CT 3-1 was 33%, with complete disappearance of starting material and a mix of products (possibly the debrominated product). The shorter reaction time is to see if we can minimise these side reactions while achieving a similar (or better) yield.