Sodium hydride → HCID 57422415, compound

HRID 658665Notes

Reaction equation

HRID 658665 reaction equation
Cl[CH2:2][CH2:3][CH2:4][NH:5][C:6]([NH:8][C:9]1[CH:10]=[N:11][N:12]([CH2:14][C:15]2[C:16]([CH3:21])=[N:17][O:18][C:19]=2[CH3:20])[CH:13]=1)=[O:7].[H-].[Na+]>CN(C=O)C>[CH3:21][C:16]1[C:15]([CH2:14][N:12]2[CH:13]=[C:9]([N:8]3[CH2:2][CH2:3][CH2:4][NH:5][C:6]3=[O:7])[CH:10]=[N:11]2)=[C:19]([CH3:20])[O:18][N:17]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 57422417HCID 57422417, compound

Product 1

HCID 57422415HCID 57422415, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(3-chloropropyl)-3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)urea (example 9-5b) (200 mg, 0.64 mmol) and 60% sodium hydride (28 mg, 0.71 mmol) in DMF (2 mL) were stirred at 0° C. for 15 minutes then allowed to warm up to room temperature and stir for 2 hours. The reaction was quenched with methanol and concentrated. The reaction was diluted with brine (50 mL) and extracted with dichloromethane (2×, 50 mL). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated. The residue was taken up in dichloromethane (5 mL) and purified by silica column chromotography (100% to 90% dichloromethane in methanol: 30 minute gradient) to afford 1-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)tetrahydropyrimidin-2(1H)-one (84 mg, 48%) as a white solid. 1H NMR (DMSO-d6, 400 MHz): δ1.85-1.91 (m, 2H), 2.10 (s, 3H), 2.37 (s, 3H), 3.12 (m, 2H), 3.48 (t, J=6.0 Hz, 2H), 5.05 (s, 2H), 6.57 (s, 1H), 7.46 (s, 1H), 7.80 (s, 1H). LC/MS; [M+H] calculated for C13H17N5O2; expected 276.14; found 276.10.

Workup

  1. customThe reaction was quenched with methanol
  2. concentrationconcentrated
  3. additionThe reaction was diluted with brine (50 mL)
  4. extractionextracted with dichloromethane (2×, 50 mL)
  5. dry with materialThe combined organic extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by silica column chromotography (100% to 90% dichloromethane in methanol: 30 minute gradient)

Sources & evidence

ORD record
ord-c37460ba3e434e88a4827dace0becdd9
Source dataset
uspto-grants-2011_12
Patent number
US08076491B2

Reaction notes

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