All Notebooks | Help | Support | About
1st December 2014 @ 11:51

Summary:

Suzuki cross-coupling on the product of TF5-1. The reaction is analogous to previous cross-couplings performed by Patrick (PT-22), and my own syntheses, TF3-1 and TF4-1.

 

Hazard and Risk Assessment:

RA TF7-1.doc

Reaction Scheme:



Procedure:

The procedure was scaled down from analogous syntheses so as to use 20mg of the thienopyrimidine starting material.
 
TF5-1 (20mg, 0.073mmol), MNR103 (24.8mg, 0.0876mmol) and PdCl2(dppf) (11.92mg, 20mol%) were placed in a sealed vessel along with IPA (1.5mL) and K2CO3 (0.15mL). The vessel was heated in a 200W microwave at 90oC for 30 mins.
 
The reaction mixture was separated dry flash chromatography to give a 12.1mg yield (0.0345mmol, 47.3%) of pale brown solid.
 
 
Data:
 
TF7-1 1H & 13C DMSO.tar
TF7-1 Nominal Mass Spec.jpg
TF7-1 Synthesis.png
TF7-1.png
TF7-1 High Res MS.jpg
 
InChi:
 
InChI=1S/C14H14N4O3S2/c15-23(20,21)10-3-1-2-9(6-10)12-7-11-13(22-12)14(16-4-5-19)18-8-17-11/h1-3,6-8,19H,4-5H2,(H2,15,20,21)(H,16,17,18)
 
 
Attached Files
1st December 2014 @ 11:05

Summary:

Suzuki cross-coupling on the product of TF6-1. The reaction is analogous to previous cross-couplings performed by Patrick (PT-22), and my own syntheses, TF3-1 and TF4-1.

 

Hazard and Risk Assessment:

RA TF8-1.doc

Reaction Scheme:



Procedure:

The procedure was scaled down from analogous syntheses so as to use 20mg of the thienopyrimidine starting material.

TF6-1 (20mg, 0.069mmol), MNR103 (23.4mg, 0.0828mmol) and PdCl2(dppf) (11.26mg, 20mol%) were placed in a sealed vessel along with IPA (1.5mL) and K2CO3 (0.15mL). The vessel was heated in a 200W microwave at 90oC for 30 mins.

The reaction mixture was purified to give a rich brown solid with a yield of 17.8mg (0.0488mmol, 70.8%). 

Data:
 
TF8-1 1H & 13C DMSO.tar
TF8-1 Nominal Mass Spec.jpg
TF8-1.png
TF8-1 Synthesis.png
TF8-1 High Res MS.jpg
 
InChi:
 
InChI=1S/C15H16N4O3S2/c16-24(21,22)11-4-1-3-10(7-11)13-8-12-14(23-13)15(19-9-18-12)17-5-2-6-20/h1,3-4,7-9,20H,2,5-6H2,(H2,16,21,22)(H,17,18,19)
 
Attached Files
26th November 2014 @ 12:41

Summary:

For this synthesis I modified the amine portion of the thienopyrimidine building block by reacting the brominated precursor (PT-19, ~600mg already in stock) with 3-aminopropan-1-ol. The product of this reaction was then cross-coupled with the sulfonamide (PT-1-18) in TF8-1.

Hazard and Risk Assessment:

RA TF6-1.doc

Reaction Scheme:

Procedure:

The procedure used was analogous to the one already performed by Alice Williamson (AEW57-2).

6-bromo-4-chlorothieno[3,2-d]pyrimidine (75mg, 0.44mmol, 1 equiv) and 3-aminopropan-1-ol (3.35 mL, 4.40mmol, 10 equiv) were stirred together at 100C for 1 hour.

The solid product was filtered through with water and collected to give a yield of 57.3mg (0.199mmol, 45.2%).

NMR spectra indicated the crude yield was sufficiently pure to be taken on as-is, as the thienopyrimidine starting material had been fully consumed in the reaction, and any residual amine was removed when the solid was filtered with water. 

Data:

TF6-1 1H & 13C DMSO Raw.tar
TF6-1 1H, 13C, D90, D135 DMSO Raw.tar
TF6-1 Nominal Mass Spec.jpg
TF6-1 Synthesis.png
TF6-1.png
TF6-1 High Res MS.jpg


InChi:

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

Attached Files
25th November 2014 @ 13:24

Summary:

For this synthesis I modified the amine portion of the thienopyrimidine building block by reacting the brominated precursor (PT-19, ~600mg remaining) with ethanolamine. The product of this reaction was then cross-coupled with the sulfonamide (PT-1-18) in TF7-1.

 

Hazard and Risk Assessment:

RA TF5-1.doc

Reaction Scheme:

Procedure:

The procedure used was analogous to the one already performed by Alice Williamson (AEW57-2).

6-bromo-4-chlorothieno[3,2-d]pyrimidine (75mg, 0.44mmol, 1 equiv) and ethanolamine (2.66 mL, 4.40mmol, 10 equiv) were stirred together at 100C for 1 hour.

The solid product was filtered through with water and collected to give a yield of 46mg (0.168mmol, 38.1%).

NMR spectra indicated the crude yield was sufficiently pure to be taken on as-is, as the thienopyrimidine starting material had been fully consumed in the reaction, and any residual amine was removed when the solid was filtered with water. 

Data:

TF5-1 1H & 13C DMSO Raw.tar
TF5-1 1H, 13C, D90, D135 DMSO Raw.tar
TF5-1 Nominal Mass Spec.jpg
TF5-1 Synthesis.png
TF5-1.png
TF5-1 High Res MS.jpg


InChi:

InChI=1S/C8H7BrN2OS/c9-7-3-6-8(13-7)5(1-2-12)10-4-11-6/h3-4,12H,1-2H2

 

Attached Files
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