Tetrahydrofuran → HCID 121393722, compound

HRID 1480030Notes

Reaction equation

HRID 1480030 reaction equation
[CH3:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=2)[C:5](=[O:17])[NH:4][C:3]=1[C:18]1[N:22]([C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=2)[N:21]=[CH:20][CH:19]=1.CC(C)([O-])C.[K+].[CH2:37]1[CH2:41]O[CH2:39][CH2:38]1.ICCCC>O>[CH2:41]([N:4]1[C:3]([C:18]2[N:22]([C:23]3[CH:24]=[CH:25][C:26]([C:27]#[N:28])=[CH:29][CH:30]=3)[N:21]=[CH:20][CH:19]=2)=[C:2]([CH3:1])[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=2)[C:5]1=[O:17])[CH2:37][CH2:38][CH3:39]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 10962Butyl iodideHCID 23665647Potassium tert-butoxideHCID 121393736HCID 121393736, compound

Product 1

HCID 121393722HCID 121393722, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

4-(5-{5-Methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1H-imidazol-4-yl}-1H-pyrazol-1-yl)benzonitrile (Example 1) (102 mg, 0.25 mmol) was added to a stirred mixture of potassium tert-butoxide (42 mg, 0.375 mmol) and THF (2.0 mL) under a nitrogen atmosphere. This resulted in the formation of a yellow solution. 1-Iodo-butane (0.057 mL, 0.5 mmol) was added and the mixture was stirred for 7 h then left to stand for 16 h. Water (10 mL) was added and the mixture was extracted with DCM (3×10 mL). The combined organic phase was dried (sodium sulfate) and concentrated in vacuo. The residue was purified by flash column chromatography (2 g Si II SPE eluted with DCM). The crude product thus obtained was further purified by flash column chromatography (2 g Si II SPE eluted with 20% EtOAc in cyclohexane). Concentration of the appropriate fractions in vacuo gave the title compound which was freeze-dried from acetonitrile/water to afford a white solid (25 mg).

Workup

  1. customThis resulted in the formation of a yellow solution
  2. waitthen left
  3. waitto stand for 16 h
  4. extractionthe mixture was extracted with DCM (3×10 mL)
  5. dry with materialThe combined organic phase was dried (sodium sulfate)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography (2 g Si II SPE eluted with DCM)
  8. customThe crude product thus obtained
  9. customwas further purified by flash column chromatography (2 g Si II SPE eluted with 20% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-fdb651bea75c48d8bab99accde375589
Source dataset
uspto-grants-2016_08
Patent number
US09409870B2

Reaction notes

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