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10th December 2014 @ 04:04
Repeat of AEW 182-1 using -OCHF2 starting material rather than -CN in the hope that this will improve solubility issues. CLogP is ~3 and LogP ~4, but this compound is being synthesised to explore the importance of the benzyl amino functional group on potency. AEW 205-1 (200 mg, 0.72 mmol, 1.00 equiv.) and AEW 180-1 (170 mg, 0.72 mmol, 1.00 equiv.) were added to toluene (3 mL) followed by potassium hydroxide (141 mg, 2.51 mmol, 3.5 equiv.) and 18-crown-6 (13 mg, 0.050 mmol, 0.07 equiv.). The reaction mixture was stirred at 40°C (bath temperature) for 30 min. TLC showed SM and new lower spot (data can't be uploaded right now but will be later). The reaction mixture was stirred for a further hour and TLC showed SM consumed (data can't be uploaded right now but will be later). The reaction was stopped and cooled before diluting with water (2- mL). The aqueous layer was extracted with EtOAc (4 x 40 mL). The combined organic layers were washed with water (2 x 20 mL), brine (20 mL), dried (MgSO4) and evaporated. The crude black product was dried in vacuo and then a crude NMR was measured. Data:   Hazard and Risk Assessment:   Strings: InChI=1S/C12H8ClFN4O/c13-10-5-15-6-11-16-17-12(18(10)11)8-1-3-9(4-2-8)19-7-14/h1-6H,7H2 and  InChI=1S/C13H19NO3/c1-13(2,3)17-12(16)14-11(9-15)10-7-5-4-6-8-10/h4-8,11,15H,9H2,1-3H3,(H,14,16) to InChI=1S/C25H26FN5O4/c1-25(2,3)35-24(32)28-20(17-7-5-4-6-8-17)15-33-22-14-27-13-21-29-30-23(31(21)22)18-9-11-19(12-10-18)34-16-26/h4-14,20H,15-16H2,1-3H3,(H,28,32)   ClC1=CN=CC2=NN=C(C3=CC=C(OCF)C=C3)N21 and OC[C@H](NC(OC(C)(C)C)=O)C1=CC=CC=C1 to FCOC(C=C1)=CC=C1C2=NN=C3C=NC=C(OC[C@H](NC(OC(C)(C)C)=O)C4=CC=CC=C4)N32
Attached Files
AEW 211-1.png
AEW 211-1.cdxml