Water → 2-[(4-{2-[(5-Ethylpyrimidin-2-yl)(4-pyridin-3-ylbenzyl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester

HRID 914495Notes

Reaction equation

HRID 914495 reaction equation
[C:1]([O:5][C:6](=[O:35])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][N:18]([CH2:27][C:28]2[CH:33]=[CH:32][C:31](Br)=[CH:30][CH:29]=2)[C:19]2[N:24]=[CH:23][C:22]([CH2:25][CH3:26])=[CH:21][N:20]=2)[N:15]=1)([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].O.O1[CH2:42][CH2:41]OCC1>C(=O)([O-])[O-].[Na+].[Na+].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>[C:1]([O:5][C:6](=[O:35])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][N:18]([C:19]2[N:24]=[CH:23][C:22]([CH2:25][CH3:26])=[CH:21][N:20]=2)[CH2:27][C:28]2[CH:33]=[CH:32][C:31]([C:13]3[CH:14]=[N:15][CH:11]=[CH:41][CH:42]=3)=[CH:30][CH:29]=2)[N:15]=1)([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 962WaterHCID 312751,4-DioxaneHCID 597592542-[(4-{2-[(4-Bromobenzyl)(5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester

Product 1

HCID 597593852-[(4-{2-[(5-Ethylpyrimidin-2-yl)(4-pyridin-3-ylbenzyl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolvent

Procedure

Under nitrogen atmosphere, 2-[(4-{2-[(4-bromobenzyl)(5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester (300 mg) synthesized in Example 402-1 and (3-diethylboryl)pyridine (76 mg) were dissolved in dioxane (2.6 mL) and sodium carbonate (2 mol/L, 1.3 mL), tetrakis(triphenylphosphine)palladium (30 mg) was added, and the mixture was refluxed for 2 hr. The reaction mixture was cooled, water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=2:1 to 1:1) to give the title compound (223 mg) as a white solid.

Workup

  1. temperaturethe mixture was refluxed for 2 hr
  2. temperatureThe reaction mixture was cooled
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=2:1 to 1:1)

Sources & evidence

ORD record
ord-64dcf668062943828501ae71c3a1102a
Source dataset
uspto-grants-2011_09
Patent number
US08026370B2

Reaction notes

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