Lithium Chloride → HCID 66748886, compound

HRID 2401749Notes

Reaction equation

HRID 2401749 reaction equation
Br[C:2]1[S:3][C:4]([C:15]2[N:19]=[CH:18][N:17]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][O:21]3)[N:16]=2)=[C:5]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[N:6]=1.C([Sn](CCCC)(CCCC)[C:31]1[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=1)CCC.[Cl-].[Li+]>O1CCOCC1.[Cu]I.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>[Cl:14][C:11]1[CH:12]=[CH:13][C:8]([CH2:7][C:5]2[N:6]=[C:2]([C:31]3[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=3)[S:3][C:4]=2[C:15]2[N:19]=[CH:18][N:17]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][O:21]3)[N:16]=2)=[CH:9][CH:10]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 27373184-(Tri-n-butylstannyl)pyridineHCID 66749521HCID 66749521, compound

Product 1

HCID 66748886HCID 66748886, compoundYield 150.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a 20 mL vial was added a solution of 3-[2-bromo-4-(4-chlorobenzyl)-1,3-thiazol-5-yl]-1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazole (0.1500 g, 0.3411 mmol) and 4-(tributylstannyl)pyridine (0.2511 g, 0.6822 mmol) in anhydrous 1,4-dioxane (5.000 mL). The solution was degassed for 10 minutes. Lithium chloride (0.108 g, 2.56 mmol) and copper (I) iodide (0.0487 g, 0.256 mmol) were added followed by tetrakis(triphenylphosphine)palladium(0) (0.0492 g, 0.0426 mmol). The reaction mixture was heated to 90° C. and allowed to stir for 18 h. The reaction was cooled to ambient temperature and quenched by the addition of a saturated aqueous solution of sodium bicarbonate (10 mL). The quench mixture was extracted with EtOAc (10 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography on silica (gradient DCM to 10% MeOH over 30 min) to afford the product (0.2245 g, 73%) as a yellow solid. LC/MS (AA) ES+ 438. 1H NMR (400 MHz, d6-DMSO) δ: 8.92 (s, 1H), 7.90 (d, J=4.8 Hz, 2H), 7.65 (d, J=1.2 Hz, 2H), 7.38-7.32 (m, 4H), 5.66 (dd, J=9.6, 2.8 Hz, 1H), 4.65 (s, 2H), 3.97-3.94 (m, 1H), 3.72-3.66 (m, 1H), 1.59-1.48 (m, 2H), 1.32-1.23 (m, 2H), 1.10-1.06 (m, 2H).

Workup

  1. customThe solution was degassed for 10 minutes
  2. temperatureThe reaction was cooled to ambient temperature
  3. customquenched by the addition of a saturated aqueous solution of sodium bicarbonate (10 mL)
  4. extractionThe quench mixture was extracted with EtOAc (10 mL×3)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by column chromatography on silica (gradient DCM to 10% MeOH over 30 min)

Sources & evidence

ORD record
ord-afee34425f164f66aa6ef28b876e9454
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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