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Chemical Structure| 871701-87-0 Chemical Structure| 871701-87-0
Chemical Structure| 871701-87-0

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GSK1790627 is the N-deacetylated metabolite of Trametinib. Trametinib is an orally active MEK inhibitor that activates autophagy and induces apoptosis. GSK1790627 is used in cancer research.

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Details of GSK1790627

CAS No. :871701-87-0
Formula : C24H21FIN5O3
M.W : 573.36
SMILES Code : O=C1N(C2=CC=CC(N)=C2)C(C(C(N1C3CC3)=O)=C(NC4=CC=C(I)C=C4F)N5C)=C(C)C5=O
English Name :1-(3-Aminophenyl)-3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione
MDL No. :MFCD34704772

Safety of GSK1790627

Application In Synthesis of GSK1790627

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 871701-87-0 ]

[ 871701-87-0 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 871701-87-0 ]
  • [ 391912-54-2 ]
  • [ 2665700-71-8 ]
YieldReaction ConditionsOperation in experiment
78% With triethylamine In N,N-dimethyl-formamide for 16h;
  • 2
  • [ 871701-87-0 ]
  • [ 1411774-27-0 ]
  • [ 2665701-13-1 ]
YieldReaction ConditionsOperation in experiment
39% With pyridine In dichloromethane at 50℃; for 16h; Inert atmosphere; Sealed tube;
  • 3
  • [ 871701-87-0 ]
  • [ 10438-96-7 ]
  • [ 2666940-97-0 ]
YieldReaction ConditionsOperation in experiment
56% With pyridine In dichloromethane for 6h;
  • 4
  • [ 871701-87-0 ]
  • [ 1807537-35-4 ]
  • [ 3023733-26-5 ]
YieldReaction ConditionsOperation in experiment
159.3 mg With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; Compound S7 TFA (562 μL, 7.3 mmol) was added to a solution of 30S9 (274.8 mg, 0.73 mmol) in CH2Cl2(7.30 mL) at room temperature. The reaction mixture was stirred for 1 h and then concentrated underreduced pressure. The crude carboxylic acid was azeotropically dried with toluene and directly usedfor the next step. iPr2EtN (64.2 μL, 0.37 mmol) was added to a suspension of the crude carboxylic acid(70.4 mg, 0.22 mmol) and 1 (105.7 mg, 0.18 mmol) and HATU (105.1 mg, 0.28 mmol) in DMF (1.84mL) at room temperature. After 5 h, the reaction mixture was diluted with EtOAc (20 mL) and washedwith saturated aqueous NaHCO3 (20 mL) and brine (20 mL). The organic layer was dried (MgSO4)and filtered. The filtrate was concentrated under reduced pressure. Column chromatography (silica,hexane/EtOAc = 1:2) afforded a yellowish solid (159.3 mg, 99%). 1H NMR (400 MHz, CDCl3): δ11.26 (s, 1H), 8.67 (s, 1H), 7.76 (d, J = 8.7 Hz, 2H), 7.66 (dd, J = 1.8, 1.8 Hz, 1H), 7.59 (dd, J = 8.0,1.1 Hz, 1H), 7.51 (dd, J = 9.6, 1.8 Hz, 1H), 7.44 (d, J = 8.7 Hz, 1H), 7.38 (dd, J = 8.0, 8.0 Hz, 1H),7.32 (d, J = 8.2 Hz, 2H), 7.06 (dd, J = 7.8, 1.4 Hz, 1H), 6.68 (dd, J = 8.3, 8.3 Hz, 1H), 4.25-4.16 (m,2H), 4.07 (s, 2H), 3.80-3.60 (m, 6H), 3.19 (s, 3H), 2.72 (tt, J = 7.3, 3.4 Hz, 1H), 2.43 (s, 3H), 1.42 (s,3H), 1.15-1.05 (m, 2H), 0.85-0.72 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 168.2, 165.0, 164.0, 155.1(d, J = 254.0 Hz), 152.0, 151.7, 145.2, 145.0, 140.5, 138.1, 134.0 (d, J = 3.8 Hz), 133.0, 130.0, 129.4,128.4 (d, J = 11.5 Hz), 128.0, 125.8 (d, J = 21.1 Hz), 125.12, 125.08, 120.4, 119.4, 103.7, 90.2, 88.0(d, J = 7.7 Hz), 71.1, 70.6, 70.4, 69.1, 69.0, 34.7, 25.3, 21.8, 13.5, 8.5; HRMS (ESI): calcd forC37H37FIN5NaO9S [M + Na]+: 896.1238, found: 896.1210.
99 % With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; 11.1 1. TsO-(III-1(m=1, n=2))-(I) Trifluoroacetic acid (562 μL) was added to a solution of tert-butyl 2-{2-[2-(tosyloxy)ethoxy]ethoxy}acetate (274.8 mg, 0.734 mmol) in CH2Cl2 (7.3 mL) at room temperature. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure to obtain a crude product of 2-{2-[2-(tosyloxy)ethoxy]ethoxy}acetic acid. To this carboxylic acid crude product (70.4 mg, 0.221 mmol), H-(I) synthesized in Synthesis Example 1 (105.7 mg, 0.184 mmol), N,N-dimethylformamide (1.84 mL), iPr2EtN (64.2 μL) , 0.369 mmol) and HATU (105.1 mg, 0.276 mmol) were added, and the mixture was stirred at room temperature for 5 hours. The reaction mixture was diluted with EtOAc (20 mL), washed successively with saturated aqueous NaHCO3 (20 mL) and saturated brine (20 mL), dried over MgSO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica, hexane/EtOAc = 1:2) to obtain TsO-(III-1(m=1, n=2))-(I) having the following structure as a yellow solid. (159.3 mg,99%).
159.3 mg With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; Compound S7 TFA (562 μL, 7.3 mmol) was added to a solution of 30S9 (274.8 mg, 0.73 mmol) in CH2Cl2(7.30 mL) at room temperature. The reaction mixture was stirred for 1 h and then concentrated underreduced pressure. The crude carboxylic acid was azeotropically dried with toluene and directly usedfor the next step. iPr2EtN (64.2 μL, 0.37 mmol) was added to a suspension of the crude carboxylic acid(70.4 mg, 0.22 mmol) and 1 (105.7 mg, 0.18 mmol) and HATU (105.1 mg, 0.28 mmol) in DMF (1.84mL) at room temperature. After 5 h, the reaction mixture was diluted with EtOAc (20 mL) and washedwith saturated aqueous NaHCO3 (20 mL) and brine (20 mL). The organic layer was dried (MgSO4)and filtered. The filtrate was concentrated under reduced pressure. Column chromatography (silica,hexane/EtOAc = 1:2) afforded a yellowish solid (159.3 mg, 99%). 1H NMR (400 MHz, CDCl3): δ11.26 (s, 1H), 8.67 (s, 1H), 7.76 (d, J = 8.7 Hz, 2H), 7.66 (dd, J = 1.8, 1.8 Hz, 1H), 7.59 (dd, J = 8.0,1.1 Hz, 1H), 7.51 (dd, J = 9.6, 1.8 Hz, 1H), 7.44 (d, J = 8.7 Hz, 1H), 7.38 (dd, J = 8.0, 8.0 Hz, 1H),7.32 (d, J = 8.2 Hz, 2H), 7.06 (dd, J = 7.8, 1.4 Hz, 1H), 6.68 (dd, J = 8.3, 8.3 Hz, 1H), 4.25-4.16 (m,2H), 4.07 (s, 2H), 3.80-3.60 (m, 6H), 3.19 (s, 3H), 2.72 (tt, J = 7.3, 3.4 Hz, 1H), 2.43 (s, 3H), 1.42 (s,3H), 1.15-1.05 (m, 2H), 0.85-0.72 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 168.2, 165.0, 164.0, 155.1(d, J = 254.0 Hz), 152.0, 151.7, 145.2, 145.0, 140.5, 138.1, 134.0 (d, J = 3.8 Hz), 133.0, 130.0, 129.4,128.4 (d, J = 11.5 Hz), 128.0, 125.8 (d, J = 21.1 Hz), 125.12, 125.08, 120.4, 119.4, 103.7, 90.2, 88.0(d, J = 7.7 Hz), 71.1, 70.6, 70.4, 69.1, 69.0, 34.7, 25.3, 21.8, 13.5, 8.5; HRMS (ESI): calcd forC37H37FIN5NaO9S [M + Na]+: 896.1238, found: 896.1210.
99 % With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; 11.1 1. TsO-(III-1(m=1, n=2))-(I) Trifluoroacetic acid (562 μL) was added to a solution of tert-butyl 2-{2-[2-(tosyloxy)ethoxy]ethoxy}acetate (274.8 mg, 0.734 mmol) in CH2Cl2 (7.3 mL) at room temperature. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure to obtain a crude product of 2-{2-[2-(tosyloxy)ethoxy]ethoxy}acetic acid. To this carboxylic acid crude product (70.4 mg, 0.221 mmol), H-(I) synthesized in Synthesis Example 1 (105.7 mg, 0.184 mmol), N,N-dimethylformamide (1.84 mL), iPr2EtN (64.2 μL) , 0.369 mmol) and HATU (105.1 mg, 0.276 mmol) were added, and the mixture was stirred at room temperature for 5 hours. The reaction mixture was diluted with EtOAc (20 mL), washed successively with saturated aqueous NaHCO3 (20 mL) and saturated brine (20 mL), dried over MgSO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica, hexane/EtOAc = 1:2) to obtain TsO-(III-1(m=1, n=2))-(I) having the following structure as a yellow solid. (159.3 mg,99%).

 

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