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

HRID 522610노트

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HRID 522610 반응식
[NH:1]1[CH:5]=[CH:4][C:3]([NH:6][C:7](=[O:9])[CH3:8])=[N:2]1.[H-].[Na+].Br.Br[CH2:14][C:15]1[C:20]([OH:21])=[CH:19][CH:18]=[CH:17][N:16]=1.BrCC1C(O)=CC=CN=1>CN(C=O)C>[OH:21][C:20]1[C:15]([CH2:14][N:1]2[CH:5]=[CH:4][C:3]([NH:6][C:7](=[O:9])[CH3:8])=[N:2]2)=[N:16][CH:17]=[CH:18][CH:19]=1

참가 물질

6

반응물 4

HCID 24758Sodium hydride2회HCID 7966402-(Bromomethyl)pyridin-3-olHCID 28278212-Bromomethyl-3-hydroxypyridine hydrobromideHCID 178474341HCID 178474341, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

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온도
0 °C

실험 절차

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 NH4CI. 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+).

후처리

  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 NH4CI
  7. dry with materialOrganic layer was dried over MgSO4 (anh)
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customResidue was purified

출처 및 근거

ORD 기록
ord-773fe2295881435f9a47fd5e5fd9652c
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09334265B2

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