Lithium Chloride → ethyl 5-(4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazol-5-yl)-1H-pyrazole-3-carboxylate

HRID 2401837Notes

Reaction equation

HRID 2401837 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1.C([Sn](CCCC)(CCCC)[C:26]1[NH:30][N:29]=[C:28]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH:27]=1)CCC.[Cl-].[Li+]>O1CCOCC1.C(OCC)(=O)C.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.[Cu]I>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][C:3]2[N:4]=[C:5]([C:7]3[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=3)[S:6][C:2]=2[C:26]2[NH:30][N:29]=[C:28]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH:27]=2)=[CH:15][CH:16]=1

Participants

8

Reactant 3

HCID 433294Lithium ChlorideHCID 149720685-Tributylstannyl-1H-pyrazole-3-carboxylic acid ethyl esterHCID 667479255-Bromo-4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazole

Product 1

HCID 66749559ethyl 5-(4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazol-5-yl)-1H-pyrazole-3-carboxylateYield 12.2%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

An argon degassed mixture of 5-bromo-4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazole (583 mg, 1.59 mmol), ethyl 5-(tributylstannyl)-1H-pyrazole-3-carboxylate (456 mg, 1.06 mmol), tetrakis(triphenylphosphine)palladium(0) (61.4 mg, 0.0531 mmol), copper(I) iodide (60.7 mg, 0.319 mmol), and lithium chloride (135 mg, 3.19 mmol) in dioxane (7.46 mL) was heated in a microwave at 150 degrees for 30 minutes. The reaction mixture was slurried in ethyl acetate (100 mL) and water (2 mL) and the mixture was filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (EA/DCM=0/100→100/0) to give the crude product. This material was purified by preparative reverse phase chromatography to give 55 mg (12% yield) of the title compound as a white solid. LC/MS (FA) ES+ 425, 427. 1H NMR (300 MHz, DMSO-d6) δ: 8.71-8.69 (m, 2H), 7.85-7.83 (m, 2H), 7.36-7.33 (m, 2H), 7.28-7.25 (m, 2H), 7.09 (s, 1H), 4.41 (s, 2H), 4.34 (q, 1H, J=7.2 Hz), 1.31 (t, 1H, J=7.2 Hz).

Workup

  1. customAn argon degassed
  2. temperaturewas heated in a microwave at 150 degrees for 30 minutes
  3. filtrationwater (2 mL) and the mixture was filtered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel chromatography (EA/DCM=0/100→100/0)
  6. customto give the crude product
  7. customThis material was purified by preparative reverse phase chromatography

Sources & evidence

ORD record
ord-2915ae6e341c41ab81cf7e6a8d84ee80
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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