Sodium hydride → HCID 69092174, 화합물

HRID 2174272노트

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HRID 2174272 반응식
[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

참가 물질

9

반응물 4

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

생성물 2

HCID 69092174HCID 69092174, 화합물HCID 69094202HCID 69094202, 화합물

시약·촉매·용매 3

HCID 702Ethanol용매HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-be4bbaa8cdd1451d91163eb3fb1b8e55
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09061030B2

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