Lithium diisopropylamide → 2-(4-(1H-pyrazol-1-yl)phenyl)-1-(4-(4-bromo-3,5-dimethoxyphenyl)thiazol-2-yl)-2-methoxyethanone

HRID 2359158Notes

Reaction equation

HRID 2359158 reaction equation
[Br:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]2[N:11]=[CH:12][S:13][CH:14]=2)=[CH:4][C:3]=1[O:15][CH3:16].[Li+].CC([N-]C(C)C)C.[N:25]1([C:30]2[CH:35]=[CH:34][C:33]([CH:36]([O:43][CH3:44])[C:37](N(OC)C)=[O:38])=[CH:32][CH:31]=2)[CH:29]=[CH:28][CH:27]=[N:26]1>C1COCC1.C1COCC1.CCCCCCC.C(C1C=CC=CC=1)C>[N:25]1([C:30]2[CH:31]=[CH:32][C:33]([CH:36]([O:43][CH3:44])[C:37]([C:12]3[S:13][CH:14]=[C:10]([C:5]4[CH:6]=[C:7]([O:8][CH3:9])[C:2]([Br:1])=[C:3]([O:15][CH3:16])[CH:4]=4)[N:11]=3)=[O:38])=[CH:34][CH:35]=2)[CH:29]=[CH:28][CH:27]=[N:26]1

Participants

6

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 584320162-(4-(1H-pyrazol-1-yl)phenyl)-N,2-dimethoxy-N-methylacetamideHCID 584320464-(4-Bromo-3,5-dimethoxyphenyl)thiazole

Product 1

HCID 584321422-(4-(1H-pyrazol-1-yl)phenyl)-1-(4-(4-bromo-3,5-dimethoxyphenyl)thiazol-2-yl)-2-methoxyethanoneYield 20%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Conditions

Temperature
-78 °C

Procedure

To a −20° C. solution of 4-(4-bromo-3,5-dimethoxyphenyl)thiazole (0.092 g, 0.305 mmol) in anhydrous THF (2 mL) under argon was added a solution of LDA (0.18 mL of a 2.0 M solution in THF/heptane/ethylbenzene, 0.37 mmol) dropwise. After stirring for 30 min, the reaction was cooled to −78° C. and a solution of 2-(4-(1H-pyrazol-1-yl)phenyl)-N,2-dimethoxy-N-methylacetamide (0.15 g, 0.55 mmol) in anhydrous THF (1.5 mL, 1.0 mL) was added dropwise. After stirring for 90 min, the mixture was quenched with brine and diluted with EtOAc. The layers were separated and the organic layer was washed with brine, dried over Na2SO4 and concentrated. Purification by chromatography (0-35% EtOAc-hexanes) gave 2-(4-(1H-pyrazol-1-yl)phenyl)-1-(4-(4-bromo-3,5-dimethoxyphenyl)thiazol-2-yl)-2-methoxyethanone as a yellow solid (0.030 g, 20% yield). MS: m/z 514.0 [M+H]+.

Workup

  1. stirringAfter stirring for 90 min
  2. customthe mixture was quenched with brine
  3. additiondiluted with EtOAc
  4. customThe layers were separated
  5. washthe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customPurification by chromatography (0-35% EtOAc-hexanes)

Sources & evidence

ORD record
ord-b95ec19f729e4afcbd31b150affba970
Source dataset
uspto-grants-2014_04
Patent number
US08685975B2

Reaction notes

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