Sodium hydride → HCID 178434730, compound

HRID 1984036Notes

Reaction equation

HRID 1984036 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C@H:12]2[CH2:17][CH2:16][C@H:15]([O:18][C:19]3[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=3)[CH2:14][CH2:13]2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[C:40](=[N:43]O)([NH2:42])[CH3:41].[H-].[Na+]>C1COCC1>[CH:1]([N:4]1[CH2:5][CH2:6][N:7]([C:10]([C@H:12]2[CH2:13][CH2:14][C@H:15]([O:18][C:19]3[CH:20]=[CH:21][C:22]([C:23]4[O:24][N:43]=[C:40]([CH3:41])[N:42]=4)=[CH:26][CH:27]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:8][CH2:9]1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 30926N-HydroxyacetamidineHCID 682631,1'-CarbonyldiimidazoleHCID 178456385HCID 178456385, compound

Product 1

HCID 178434730HCID 178434730, compoundYield 44.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 0.1 g (0.22 mmol) of trans-4-[4-(4-Isopropyl-piperazine-1-carbonyl)-cyclohexyloxy]-benzoic acid and 59 mg (0.36 mmol) of 1,1′-carbonyl-diimidazole in 2 ml THF was refluxed for 16 hr. After cooling down, 79 mg (1.1 mmol) of acetamide oxime was added and the mixture was refluxed for 48 hr. To the mixture, 29 mg (0.66 mmol, 55% purity) of sodium hydride was added and the mixture was refluxed for 16 hr. The mixture was evaporated. The mixture was diluted with AcOEt, washed with saturated NaHCO3 solution, dried over Na2SO4, and evaporated. The residue was purified by column chromatography on silica eluting with dichloromethane and methanol=from 98:2 to 9:1. The combined product fractions were evaporated to dryness to yield 40 mg (44%) of the title compound. MS (m/e): 413.2 (MH+).

Workup

  1. temperaturewas refluxed for 16 hr
  2. temperatureAfter cooling down
  3. temperaturethe mixture was refluxed for 48 hr
  4. temperaturethe mixture was refluxed for 16 hr
  5. customThe mixture was evaporated
  6. additionThe mixture was diluted with AcOEt
  7. washwashed with saturated NaHCO3 solution
  8. dry with materialdried over Na2SO4
  9. customevaporated
  10. customThe residue was purified by column chromatography on silica eluting with dichloromethane and methanol=from 98:2 to 9:1
  11. customThe combined product fractions were evaporated to dryness

Sources & evidence

ORD record
ord-5e804e64f84347a088582aa063199216
Source dataset
uspto-grants-2009_06
Patent number
US07544683B2

Reaction notes

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