Sodium hydride → N-{1-[(6-methyl-2-pyridinyl)methyl]-1H-pyrazol-3-yl}acetamide

HRID 522609ノート

反応式

HRID 522609 の反応式
[NH:1]1[CH:5]=[CH:4][C:3]([NH:6][C:7](=[O:9])[CH3:8])=[N:2]1.[H-].[Na+].Br[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[N:15]=1>C1COCC1>[CH3:13][C:14]1[N:15]=[C:16]([CH2:20][N:1]2[CH:5]=[CH:4][C:3]([NH:6][C:7](=[O:9])[CH3:8])=[N:2]2)[CH:17]=[CH:18][CH:19]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 125437332-(Bromomethyl)-6-methylpyridineHCID 178474341HCID 178474341、化合物

生成物 1

HCID 86691608N-{1-[(6-methyl-2-pyridinyl)methyl]-1H-pyrazol-3-yl}acetamide収率 75%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

Intermediate 1 (97 mg, 0.774 mmol) was dissolved in 8 mL of THF (anh), at 0° C. NaH (ALDRICH, 31 mg, 0.774 mmol) was added, and mixture of reaction was stirred at 0° C. for 30 minutes. A solution of Intermediate 11 (144 mg, 0.774 mmol) in 2 mL THF (anh) was added to the mixture. Reaction was heated at 75° C. overnight. Mixture of reaction was partitioned between distilled water, EtOAc (×3) and DCM. Organic layers were dried over MgSO4 (anh) and filtered. Solvent was evaporated under vacuum. Residue was purified by silica chromatography column using a linear gradient of DCM/MeOH as eluents to give the title compound (133 mg, 0.578 mmol, 75% yield). 1H NMR (300 MHz, DMSO-d6) ppm: 10.40 (br s, 1H), 7.72 (d, 1H), 7.60-7.66 (m, 1H), 7.17-7.16 (m, 1H), 6.74-6.77 (m, 1H), 6.49 (d, 1H), 5.24 (s, 2H), 2.44 (s, 3H), 1.95 (s, 3H). [ES+MS] m/z 231 (MH+).

後処理

  1. additionmixture of reaction
  2. customReaction
  3. temperaturewas heated at 75° C. overnight
  4. additionMixture of reaction
  5. customwas partitioned
  6. distillationbetween distilled water, EtOAc (×3) and DCM
  7. dry with materialOrganic layers were dried over MgSO4 (anh)
  8. filtrationfiltered
  9. customSolvent was evaporated under vacuum
  10. customResidue was purified by silica chromatography column

出典と根拠

ORDレコード
ord-dacca3c64840402392333b83763af68f
出典データセット
uspto-grants-2016_05
特許番号
US09334265B2

反応ノート

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