Water → 2-(3,4-Dimethoxy-phenyl)-5-(3-fluoro-4-methanesulfonyl-phenyl)-6-methyl-imidazo[2,1-b][1,3,4]thiadiazole

HRID 2409530Notes

Reaction equation

HRID 2409530 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][C:17]([CH3:20])=[C:18](I)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[F:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][C:27]=1[S:28]([CH3:31])(=[O:30])=[O:29].C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][C:17]([CH3:20])=[C:18]([C:24]4[CH:25]=[CH:26][C:27]([S:28]([CH3:31])(=[O:29])=[O:30])=[C:22]([F:21])[CH:23]=4)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 459336283-Fluoro-4-(methylsulphonyl)benzeneboronic acidHCID 667169392-(3,4-Dimethoxy-phenyl)-5-iodo-6-methyl-imidazo[2,1-b][1,3,4]thiadiazole

Product 1

HCID 667169102-(3,4-Dimethoxy-phenyl)-5-(3-fluoro-4-methanesulfonyl-phenyl)-6-methyl-imidazo[2,1-b][1,3,4]thiadiazoleYield 25.7%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 2-(3,4-dimethoxy-phenyl)-5-iodo-6-methyl-imidazo[2,1-b][1,3,4]thiadiazole (0.035 g, 0.087 mmol, 1 eq) in dioxane (1.8 mL), 3-fluoro-4-(methylsulfonyl)phenylboronic acid (0.047 g, 0.217 mmol, 2.5 eq), Pd(Ph3P)2Cl2 (0.006 g, 0.0087 mmol, 0.1 eq), potassium carbonate (0.06 g, 0.435 mmol, 5 eq) and water (0.8 mL) were added. The reaction mixture was subjected to MW irradiation (120° C., 35 min, 200 W), cooled to RT and concentrated. The residue was purified by silica gel chromatography (0-0.5% MeOH in DCM). Product fractions afforded an oily residue that was further purified by trituration with Et2O providing a pale yellow solid (0.02 g) and by preparative HPLC to give the pure product (0.010 g, 25%). HPLC-MS: (50-100% B in 8 min, 0.6 mL/min): tR=2.41 min, [M+H]+ m/z 448.1. 1H NMR (300 MHz, CDCl3) δ/ppm 8.03 (dd, J=8.3, 7.7, 1H), 7.81-7.70 (m, 2H), 7.39 (dt, J=3.4, 2.0, 2H), 6.94 (d, J=8.2, 1H), 3.96 (s, 3H), 3.94 (s, 3H), 3.26 (s, 3H), 2.59 (s, 3H).

Workup

  1. additionwere added
  2. customThe reaction mixture was subjected to MW irradiation (120° C., 35 min, 200 W)
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography (0-0.5% MeOH in DCM)
  5. customProduct fractions afforded an oily residue that
  6. customwas further purified by trituration with Et2O providing a pale yellow solid (0.02 g)

Sources & evidence

ORD record
ord-3893d1d8f19c419b9379719668a7b358
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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