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27th November 2013 @ 20:13

Synthesis of 7-methylthieno[3,2-d]pyrimidin-4-amine (PT-16) was scaled up by a factor of ten with some modifications.

 

 

4-chloro-7-methylthieno[3,2-d]pyrimidine (100 mg) was suspended in concentrated ammonium hydroxide (5 ml) and n-butanol (2 ml) and stirred at 80°C for 16 hours in a sealed tube. TLC indicated 

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27th November 2013 @ 14:23

 

4-chloro-7-methylthieno[3,2-d]pyrimidine (10mg) was suspended in concentrated ammonium hydroxide (1ml) and stirred at 80°C for 16 hours in a sealed tube. TLC indicated completion (EtOAc) and the solvents were removed in vacuo to give the product and ammonium chloride (15 mg, >99%). NMR (CDCl3) indicated complete consumption of SM and conversion to a single new product. Reaction was scaled up Synthesis of 7-methylthieno[3,2-d]pyrimidin-4-amine (PT-17).

NMR (dmso) matched with literature (page 70), with a known impurity (triplet, 7.17) due to cross-contaminated NMR solvent.

PT-1-16 1H DMSO aromatic region.png
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11th November 2013 @ 03:48

Repeat of AEW 100-4 with monitoring after 2 h

Procedure:

AT-5 (100 mg, 0.4 mmol, 1.0 equiv.), isopropanol (2 mL) and ammonia (4 mL) were stired in a sealed tube and then heated to 120 ˚C [blast shield in place] for 2 hours 


Data:

 

Hazard and Risk Assessment:

See: Amination of bromochlorothienopyrimidine (AT-6-4) 

InChi:

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)

5th November 2013 @ 06:18

A solution of 3-bromobenzenesulfonyl chloride (0.28 mL, 1.96 mmol, 1 equiv.) in THF (3 mL) was cooled to 0 ˚C. N,N-dimethylethylenediamine (0.535 mL, 4.9 mmol, 2.5 equiv. mmol) was added dropwise at 0 ˚C and the reaction mixture was stirred o/n whilst reaching room temperature. Reaction complete.

EtOAc (5 mL) added and then 1M HCl (5 mL). Aqueous layers extracted with EtOAC (2 x 5 mL), then combined organic layers washed with water (5 mL), brine (5 mL), dried (MgSO4), filtered and evaporated to yield a pale oil that crystallised to a white solid at the high vac xx mg and used as crude in next step. High purity by 1H NMR.

Data: 

 

1H NMR (xx MHz, CDCl3): δ

 

Hazard and Risk Assessment:

See Synthesis of 3-bromo-N-methylbenzenesulfonamide (AEW 68-1) but with N,N-dimethylethylenediamine which is a highly flammable liquid and vapour; harmful if swallowed; causes severe burns and eye damage.

 

InChi:

InChI=1S/C6H4BrClO2S/c7-5-2-1-3-6(4-5)11(8,9)10/h1-4H

to

InChI=1S/C10H15BrN2O2S/c1-13(2)7-6-12-16(14,15)10-5-3-4-9(11)8-10/h3-5,8,12H,6-7H2,1-2H3

4th November 2013 @ 23:22

Repeat of AEW 100-3 with monitoring after 4 h

Procedure:

AT-5 (200 mg, 0.8 mmol, 1.0 equiv.), isopropanol (4 mL) and ammonia (8 mL) were stired in a sealed tube and then heated to 120 ˚C [blast shield in place] for 4 hours 


Data:

AEW 100-2 crude reaction - SM.pdf
AEW 100-2 crude reaction - SM.mnova
AEW 100-2.zip

Hazard and Risk Assessment:

See: Amination of bromochlorothienopyrimidine (AT-6-4) 

InChi:

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)