1-Methyl-2-(tributylstannyl)-1H-imidazole → Trifluoroacetic acid

HRID 926625Notes

Reaction equation

HRID 926625 reaction equation
[CH2:1]([C:8]1[C:9](Cl)=[N:10][C:11]2[C:16]([C:17]=1[Cl:18])=[CH:15][C:14]([C:19]([C:31]1[N:35]([CH3:36])[CH:34]=[N:33][CH:32]=1)([C:21]1[CH:22]=[N:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=1)[OH:20])=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:38]([OH:44])([C:40]([F:43])([F:42])[F:41])=[O:39].[CH3:45][N:46]1[CH:50]=[CH:49][N:48]=[C:47]1[Sn](CCCC)(CCCC)CCCC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[CH2:1]([C:8]1[C:9]([C:47]2[N:46]([CH3:45])[CH:50]=[CH:49][N:48]=2)=[N:10][C:11]2[C:16]([C:17]=1[Cl:18])=[CH:15][C:14]([C:19]([C:31]1[N:35]([CH3:36])[CH:34]=[N:33][CH:32]=1)([C:21]1[CH:22]=[N:23][C:24]([C:27]([F:30])([F:28])[F:29])=[CH:25][CH:26]=1)[OH:20])=[CH:13][CH:12]=2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[C:38]([OH:44])([C:40]([F:43])([F:42])[F:41])=[O:39].[C:38]([OH:44])([C:40]([F:43])([F:42])[F:41])=[O:39]

Participants

6

Reactant 2

HCID 27632521-Methyl-2-(tributylstannyl)-1H-imidazoleHCID 131735025HCID 131735025, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 131735026HCID 131735026, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of (3-benzyl-2,4-dichloroquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol (1.01 g, 1.86 mmol, Example 109), 1-methyl-2-(tributylstannyl)-1H-imidazole (1.42 g, 3.68 mmol), Pd(PPh3)4 (206 mg, 0.180 mmol), and toluene (10 mL) was sparged with N2 for about 10 minutes, then heated at 83° C. for 16 hours and 110° C. for 3 hours. After cooling down to room temperature, the mixture was concentrated in vacuo and DCM was added. The precipitated solid was filtered and dissolved in DMSO and MeOH. A few drops of TFA were added to improve solubility. The mixture was purified by reverse phase HPLC (water/acetonitrile/0.1% TFA) to provide the title compound as a TFA salt. 1H NMR (400 MHz, MeOH-d4) δ 9.06 (s, 1H), 8.94 (s, 1H), 8.86 (d, J=2.02 Hz, 1H), 8.54 (d, J=2.02 Hz, 1H), 8.22 (d, J=9.09 Hz, 1H), 8.16 (dd, J=2.02, 8.08 Hz, 1H), 7.90-7.94 (m, 2H), 7.64 (d, J=1.52 Hz, 1H), 7.19-7.26 (m, 3H), 7.18 (d, J=1.52 Hz, 1H), 6.86-6.90 (m, 2H), 4.54 (s, 2H), 3.74 (s, 3H), 3.47 (s, 3H).

Workup

  1. customwas sparged with N2 for about 10 minutes
  2. temperatureAfter cooling down to room temperature
  3. concentrationthe mixture was concentrated in vacuo and DCM
  4. additionwas added
  5. filtrationThe precipitated solid was filtered
  6. dissolutiondissolved in DMSO
  7. additionA few drops of TFA were added
  8. customThe mixture was purified by reverse phase HPLC (water/acetonitrile/0.1% TFA)

Sources & evidence

ORD record
ord-a541816ff33e4bd1a9bef269e153efdf
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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