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1st December 2014 @ 11:51

Summary:

In this reaction I will perform a Suzuki cross-coupling on the product of TF5-1. The reaction is analogous to previous cross-couplings performed by Patrick, 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
 
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:

In this reaction I will perform a Suzuki cross-coupling on the product of TF6-1. The reaction is analogous to previous cross-couplings performed by Patrick, 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
 
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 (~600mg already in stock) with 3-aminopropan-1-ol.

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


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 (~600mg already in stock) with ethanolamine.

 

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


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
20th October 2014 @ 07:50

Summary:

Synthesis of the double-methylated compound was attempted. The procedure used was analogous to that of TF3-1 and PT-22.

Hazard and Risk Assessment:

RA TF4-1.doc

Reaction Scheme:

Procedure:

The procedure was analogous to the syntheses of TF3-1 and PT-22, using the methylated boronic acid pinocol ester instead (which was fortunately in stock).

6-bromo-7-methylthieno[3,2-d]pyrimidin-4-amine [TF2] (17.05 mg, 1 eq), methylated MNR-103 (28.3 mg, 1.2 eq) and Pd(dppf)Cl2 (9.64 mg, 20mol%) were dissolved in isopropyl alcohol (1.2 mL). Potassium carbonate solution (1M, 0.36 mL) was added.

The reaction was heated to 90°C for 30 minutes under microwave irradiation in a sealed vessel.

The product was then purified using column chromatography (0-10% methanol in chloroform for 20 tubes) and evaporated to dryness to give a yield of ~24mg of pale brown product. The solid was soluble in methanol, moreso than the previous product (TF3-1).

Data:

TF4-1 1H MeOD Crude.pdf
TF4-1 1H MeOD.pdf
TF4-1 13C MeOD.pdf
TF4-1 COSY MeOD.pdf
TF4-1 HMBC MeOD.pdf
TF4-1 HSQC MeOD.pdf
TF4-1 DEPT-135 MeOD.pdf
TF4-1 NOESY MeOD.pdf
TF4-1 Raw.tar
TF4-1 Accurate Mass Spec.jpg
TF4-1 Nominal Mass Spec Zoomed.jpg
TF4-1 Nominal Mass Spec.jpg

InChi:

InChI=1S/C14H14N4O2S2/c1-7-3-4-9(22(16,19)20)5-10(7)12-8(2)11-13(21-12)14(15)18-6-17-11/h3-6H,1-2H3,(H2,15,17,18)(H2,16,19,20)

Attached Files