Sodium hydride → HCID 69092174, compound

HRID 2174272Notes

Reaction equation

HRID 2174272 reaction equation
[O:1]1[CH:5]=[C:4]([C:6]([NH:8][NH2:9])=O)[N:3]=[CH:2]1.Cl.[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17](=[NH:19])[NH2:18].[H-].[Na+].Br[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[F:30]>C(O)C.CN(C)C=O.O>[F:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[CH2:23][N:8]1[C:6]([C:4]2[N:3]=[CH:2][O:1][CH:5]=2)=[N:19][C:17]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][N:11]=2)=[N:9]1.[F:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[CH2:23][N:9]1[C:17]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][N:11]=2)=[N:18][C:6]([C:4]2[N:3]=[CH:2][O:1][CH:5]=2)=[N:8]1

Participants

9

Reactant 4

HCID 24758Sodium hydrideHCID 67968alpha-Bromo-o-fluorotolueneHCID 12403615Pyridine-2-carboximidamide hydrochlorideHCID 497617151,3-Oxazole-4-carbohydrazide

Product 2

HCID 69092174HCID 69092174, compoundHCID 69094202HCID 69094202, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of oxazole-4-carbohydrazide (228 mg, 1.794 mmol) in ethanol (8.9 mL) was added picolinimidamide hydrochloride (283 mg, 1.79 mmol). After heating the orange solution at 100° C. for 50 h, the solvent was removed in vacuo and the residue was azeotroped with toluene (2×4 mL) to give 514 mg of crude material. 187 mg of the crude material (0.75 mmol) was dissolved in N,N-dimethylformamide (3.7 mL) and treated with sodium hydride (60% dispersion in mineral oil, 75 mg, 1.9 mmol) in a single portion at ambient temperature. After stirring for 20 min, 1-(bromomethyl)-2-fluorobenzene (0.136 mL, 1.12 mmol) was added. The solution was stirred for an additional 45 min, at which point the solution was poured into water (75 mL) and extracted with ethyl acetate (3×50 mL). The organics were combined, washed with water (2×50 mL) and brine (1×50 mL), dried over magnesium sulfate, filtered, and the solvent was removed in vacuo to give the crude product as an orange oil. Purification by silica gel chromatography (10-100% ethyl acetate in hexanes) provided 4-(1-(2-fluorobenzyl)-3-(pyridin-2-yl)-1H-1,2,4-triazol-5-yl)oxazole, I-12 (58 mg, 0.18 mmol, 24% yield over two steps) as a tan solid and 4-(1-(2-fluorobenzyl)-5-(pyridin-2-yl)-1H-1,2,4-triazol-3-yl)oxazole, I-13 (21 mg, 0.06 mmol, 8.7% yield over two steps) as a brown solid.

Workup

  1. customthe solvent was removed in vacuo
  2. customthe residue was azeotroped with toluene (2×4 mL)
  3. customto give 514 mg of crude material
  4. stirringThe solution was stirred for an additional 45 min, at which point the solution
  5. extractionextracted with ethyl acetate (3×50 mL)
  6. washwashed with water (2×50 mL) and brine (1×50 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customthe solvent was removed in vacuo
  10. customto give the crude product as an orange oil
  11. customPurification by silica gel chromatography (10-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-be4bbaa8cdd1451d91163eb3fb1b8e55
Source dataset
uspto-grants-2015_06
Patent number
US09061030B2

Reaction notes

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