Dimethylformamide → N-{1-[(3-hydroxy-2-pyridinyl)methyl]-1H-pyrazol-3-yl}acetamide

HRID 1467909ノート

反応式

HRID 1467909 の反応式
CC([N:5]([C:9]1SC=[C:12]([CH2:14]Br)[N:13]=1)C(=O)[O-])(C)C.[H-].[Na+].Br.Br[CH2:20][C:21]1[C:26]([OH:27])=[CH:25][CH:24]=[CH:23][N:22]=1.Br[CH2:29][C:30]1C(O)=CC=C[N:31]=1.CN(C=[O:41])C>>[OH:27][C:26]1[C:21]([CH2:20][N:31]2[CH:30]=[CH:29][C:9]([NH:13][C:12](=[O:41])[CH3:14])=[N:5]2)=[N:22][CH:23]=[CH:24][CH:25]=1

参加物

6

反応物 5

HCID 6228Dimethylformamide2 回HCID 24758Sodium hydride2 回HCID 7966402-(Bromomethyl)pyridin-3-olHCID 28278212-Bromomethyl-3-hydroxypyridine hydrobromideHCID 1317326971,1-Dimethylethyl[4-(bromomethyl)-1,3-thiazol-2-yl]carbamate

生成物 1

HCID 86691609N-{1-[(3-hydroxy-2-pyridinyl)methyl]-1H-pyrazol-3-yl}acetamide収率 13%

反応条件

温度
0 °C

実験手順

Intermediate 1 (200 mg, 1.598 mmol) was dissolved in 2 mL of anhydrous DMF at 0° C. Sodium hydride (ALDRICH, 48.5 mg, 1.920 mmol) was added and mixture of reaction was stirred at 0° C. for 20 minutes. 2-(Bromomethyl)-3-pyridinol hydrobromide (ALFAAESAR, 301 mg, 1.598 mmol) was dissolved in 2 mL of DMF (anh) at 0° C. Sodium hydride (ALDRICH, 48.5 mg, 1.920 mmol) was added and this solution was stirred at 0° C. for 20 minutes. Solution of 2-(bromomethyl)-3-pyridinol was added dropwise to reaction mixture. Reaction was stirred at 80° C. for 24 h. Solvent was evaporated to dryness. Residue was partitioned between EtOAc and NH4Cl. Organic layer was dried over MgSO4 (anh), filtered and concentrated to dryness. Residue was purified using silica chromatography column using a linear gradient of DCM/MeOH as eluents to give the title compound (48.5 mg, 0.207 mmol, 13% yield). 1H NMR (300 MHz, CDCl3) δ ppm: 9.70 (br s, 1H), 8.04 (m, 1H), 7.46 (d, 1H), 7.33 (m, 1H), 7.24 (m, 1H), 6.53 (d, 1H), 5.42 (s, 2H), 2.27 (s, 3H). [ES+MS] m/z 233 (MH+).

後処理

  1. additionmixture of reaction
  2. stirringthis solution was stirred at 0° C. for 20 minutes
  3. customReaction
  4. stirringwas stirred at 80° C. for 24 h
  5. customSolvent was evaporated to dryness
  6. customResidue was partitioned between EtOAc and NH4Cl
  7. dry with materialOrganic layer was dried over MgSO4 (anh)
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customResidue was purified

出典と根拠

ORDレコード
ord-d815ba64b59e422eb617150588234302
出典データセット
uspto-grants-2015_04
特許番号
US09000181B2

反応ノート

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