Dimethylformamide → 3-[7-thiophen-2-yl-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester

HRID 2089532Notes

Reaction equation

HRID 2089532 reaction equation
[CH:1]([O:4][C:5]([C:7]1[N:8]([CH:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19](Br)[CH:20]=3)[CH2:15][CH2:14][CH2:13]2)[CH:9]=[N:10][CH:11]=1)=[O:6])([CH3:3])[CH3:2].[S:23]1[CH:27]=[CH:26][CH:25]=[C:24]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].CN(C=O)C>O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:1]([O:4][C:5]([C:7]1[N:8]([CH:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([C:24]4[S:23][CH:27]=[CH:26][CH:25]=4)[CH:20]=3)[CH2:15][CH2:14][CH2:13]2)[CH:9]=[N:10][CH:11]=1)=[O:6])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 27339602-Thiopheneboronic acidHCID 591994563-(7-bromo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester

Product 1

HCID 591994353-[7-thiophen-2-yl-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A flask is charged with 3-(7-bromo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester (0.225 g, 0.520 mmol), which can be prepared as described in Example 5, 2-thienylboronic acid (0.145 g, 1.041 mmol), aqueous sodium carbonate (2M, 1.30 mL, 2.60 mmol) and DMF (35 mL). Tetrakis(triphenylphosphine) palladium (0.060 g, 0.052 mmol) is added and the mixture is heated to 150° C. in a sealed tube under microwave irradiation conditions for 12 minutes. The reaction is then cooled to room temperature, diluted with water and extracted with dichloromethane. The organic phase is dried over sodium sulfate, filtered, and concentrated to give a residue, which is purified by silica gel chromatography (hexanes-ethyl acetate mixtures) to give 3-[7-thiophen-2-yl-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester. MS: (ESI) m/z 367.2 (M+H)+. The HCl salt of the title compound can be prepared by dissolution in diethyl ether followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 3-[7-thiophen-2-yl-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester; 1H NMR (400 MHz, MeOD) δ ppm 1.38 (d, J=6.3 Hz, 3 H), 1.41 (d, J=6.3 Hz, 3 H), 1.80-1.97 (m, 2 H), 2.22-2.34 (m, 2 H), 2.86-2.94 (m, 1 H), 3.04 (dt, J=17.2, 6.0 Hz, 1 H), 5.26 (d, J=6.3 Hz, 1 H), 6.36 (t, J=5.6 Hz, 1 H), 7.06 (dd, J=5.2, 3.7 Hz, 1 H), 7.18 (br. s, 1 H), 7.28 (dd, J=3.7, 1.1 Hz, 1 H), 7.30 (d, J=8.1 Hz, 1 H), 7.34 (dd, J=5.2, 1.1 Hz, 1 H), 7.48 (s, 1 H), 7.58 (dd, J=8.1, 2.0 Hz, 1 H), 7.77 (d, J=1.0 Hz, 1 H).

Workup

  1. customcan be prepared
  2. temperatureThe reaction is then cooled to room temperature
  3. extractionextracted with dichloromethane
  4. dry with materialThe organic phase is dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue, which
  8. customis purified by silica gel chromatography (hexanes-ethyl acetate mixtures)

Sources & evidence

ORD record
ord-2d4e9b83ccb747c6a9d126b8ead40a3a
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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