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

HRID 1467909Notes

Reaction equation

HRID 1467909 reaction equation
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

Participants

6

Reactant 5

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

Product 1

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

Conditions

Temperature
0 °C

Procedure

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+).

Workup

  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

Sources & evidence

ORD record
ord-d815ba64b59e422eb617150588234302
Source dataset
uspto-grants-2015_04
Patent number
US09000181B2

Reaction notes

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