ChemicalBook CAS DataBase List I-BET151 (GSK1210151A)

I-BET151 (GSK1210151A) synthesis

9synthesis methods

Product Name:I-BET151 (GSK1210151A)
CAS Number:1300031-49-5
Molecular formula:C23H21N5O3
Molecular Weight:415.44

3-QuinolinecarboxaMide, 7-(3,5-diMethyl-4-isoxazolyl)-6-Methoxy-4-[[(1R)-1-(2-pyridinyl)ethyl]aMino]-

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Yield: 77%

Reaction Conditions:

with [bis(acetoxy)iodo]benzene;potassium hydroxide in methanol for 1.33333 h;Cooling with ice;Hofmann rearrangement;

Steps:

7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-(2-pyridinyl)ethyl]-1,3-dihydro-2-Himidazo[4,5c]quinolin-2-one (I-BET151)
7-(3,5-Dimethyl-4-isoxazolyl)-6-(methyloxy)-4-{[(1R)-1-(2-pyridinyl)ethyl]amino}-3-quinolinecarboxamide (45 g, 102 mmol) was dissolved in methanol (500 mL) and potassium hydroxide (7.47 g, 133 mmol) was added. The mixture was stirred in an ice bath, then iodobenzene diacetate (39.6 g, 123 mmol) was added in small portions over 20 min and the mixture stirred for a further 1 h. The solvent was evaporated in vacuo, the residue diluted with water (1 L), and the resulting gummy suspension extracted with DCM (2 x 300 mL). The solvent was dried (sodium sulphate) and loaded directly onto a silica column (750 g), which was then eluted with a 2M ammonia in methanol / DCM gradient (0-10%). After evaporation of solvents in vacuo 7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-(2-pyridinyl)ethyl]-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one (32.7 g, 77% yield) was obtained as a beige solid. ¹H-NMR (600 MHz, DMSO-d6) d ppm 2.03 (d, J=6.5 Hz, 3 H), 2.04 (s, 3 H), 2.25 (s, 3 H), 3.46 (bs, 3 H), 6.26 (q, J=7.1 Hz, 1 H), 6.69 (bs, 1 H), 7.35 (dd, J=7.0, 5.1 Hz, 1 H), 7.41 (d, J=6.6 Hz, 1 H), 7.76-7.79 (m, 1 H), 7.79 (s, 1 H), 8.59-8.65 (m, 2 H), 11.77 (bs, 1H). ¹³C NMR (151 MHz, DMSO-d6) d ppm 10.3, 11.3, 17.6, 51.8, 55.5, 100.8, 112.0, 115.4, 120.2, 121.0, 122.7, 122.7, 128.1, 132.3, 132. 8, 137.6, 139.8, 149.3, 154.3, 154.5, 159.0, 159.2, 166.0. MS (Method HpH): MH⁺ 416, Rt 0.85 min. HRMS (m/z): [MH]⁺ calcd for C₂₃H₂₂N₅O₃ 416.1723; found 416.1718.

References:

Mirguet, Olivier;Lamotte, Yann;Donche, Frédéric;Toum, Jérôme;Gellibert, Franoise;Bouillot, Anne;Gosmini, Romain;Nguyen, Van-Loc;Delannée, Delphine;Seal, Jonathan;Blandel, Florence;Boullay, Anne-Bénédicte;Boursier, Eric;Martin, Sandrine;Brusq, Jean-Marie;Krysa, Gael;Riou, Alizon;Tellier, Rémi;Costaz, Agns;Huet, Pascal;Dudit, Yann;Trottet, Lionel;Kirilovsky, Jorge;Nicodeme, Edwige [Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,# 8,p. 2963 - 2967] Location in patent:supporting information; experimental part