Compounds as inhibitors of diacylglycerol O-acyltransferase type 1 enzyme
A compound and solvate technology, applied in the field of novel compounds, can solve problems such as small homology
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[0165] The preparation of compounds of formulas B and C is depicted in the following schemes.
[0166] Compounds of formula B are either commercially available or can be conveniently prepared by a variety of methods familiar to those skilled in the art. A common route is shown in Scheme 2.
[0167] Compounds of formula D as starting materials in solvents such as dichloromethane can be used in solvents such as toluene at 0°C with Me 3 Al solution treatment. The mixture thus obtained can be treated with an amino derivative of formula E in a solvent such as dichloromethane followed by an acid such as 1N HCl to prepare an intermediate of formula F.
[0168] Scenario 2
[0169]
[0170] in,
[0171] R 11 and W have the same meanings as defined above.
[0172] Compounds of formula H are either commercially available or can be conveniently prepared by a variety of methods familiar to those skilled in the art. A common route is shown in Scheme 3.
[0173] Compounds of for...
Embodiment 1
[0477]
[0478] 2-((1r,4r)-4-(4-(2-((4-(trifluoromethoxy)benzyl)carbamoyl) Imidazo[1,2-a]pyridin-6-yl ) phenyl) cyclohexyl) acetic acid -Compound 1
[0479]
[0480] Step A: 2-((1r,4r)-4-(4-(2-((4-(trifluoromethoxy)benzyl)carbamoyl)imidazolo [1,2-a]lpyridin-6-yl)phenyl)cyclohexyl)ethyl acetate
[0481] At room temperature, the intermediate LXV2-((1r,4r)-4-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolane-2- Complexation of ethyl) phenyl) cyclohexyl) ethyl acetate (452 mg, 1.21 mmol), [1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium (II) and dichloromethane (82.7mg, 0.10mmol) and tripotassium phosphate (430mg, 20.2mmol) were successively added to intermediate I6-bromo-N-(4-(trifluoromethoxy)benzyl)imidazo[1,2-a ] Pyridine-2-carboxamide (420 mg, 1.01 mmol) in a solution (15 ml) in a solvent mixture (15 ml) of 1,4-dioxane and water (10:1 (v / v)). The reaction mixture was stirred at 90 °C for 20 hours. After cooling to room temperature, the reaction mixture w...
Embodiment 2
[0487]
[0488] 2-(1r,4r)-4-(4-(2-((4-(trifluoromethyl)phenyl)carbamoyl)imidazo[1,2-a]pyridin-6-yl) Phenyl)cyclohexyl)acetic acid -Compound 2
[0489]
[0490] Step A: 2-((1r,4r)-4-(4-(2-(4-(Trifluoromethyl)phenyl)carbamoyl)imidazo[1,2-a]- Pyridin-6-yl)phenyl)cyclohexyl)ethyl acetate
[0491] Following essentially the same procedure as described in Example 1, Step A, the title compound was prepared from Intermediate II and Intermediate LXV.
[0492] 1 H NMR (400MHz, CDCl 3 )δ9.41(s,1H),8.32(s,1H),8.27(s,1H),7.90(d,2H),7.64(t,3H),7.50(d,2H),7.33(d,2H ),4.11(q,2H),2.54(t,2H),2.22(d,2H),1.94-1.82(m,6H),1.73(q,2H),1.21(t,3H),1.12(q, 2H).MS 550.1(M+1) + .
[0493] Step B: 2-((1r,4r)-4-(4-(2-((4-(trifluoromethyl)phenyl)carbamoyl)imidazo[1,2-a] Pyridin-6-yl)phenyl)cyclohexyl)acetic acid
[0494] Compound 2 was prepared essentially following the same procedure as described in Example 1, Step B.
[0495] 1 H NMR (400MHz, DMSO-d 6 )δ10.76(s,1H),8.96(s,1H),8.56...
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