Sodium hydride → HCID 178456381, compound

HRID 1984024Notes

Reaction equation

HRID 1984024 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]([OH:18])[CH2:14][CH2:13]2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[H-].[Na+].Cl[C:22]1[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][N:23]=1.C([O-])(O)=O.[Na+]>CC(N(C)C)=O>[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C@H:12]2[CH2:13][CH2:14][C@H:15]([O:18][C:22]3[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][N:23]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 178456388HCID 178456388, compound2×

Product 1

HCID 178456381HCID 178456381, compoundYield 11.7%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a mixture of 200 mg (0.79 mmol) of trans-(4-isopropyl-piperazin-1-yl)-(4-hydroxy-cyclohexyl)-methanone (Intermediate 4) in 1 ml of DMA, 42 mg (0.96 mmol) of sodium hydride was added at room temperature and stirred for 30 min. To the mixture, 220 mg (1.59 mmol) of 6-chloronicotinonitrile (commercially available) was added and stirred at 100° C. for 24 h. The mixture was poured into saturated NaHCO3 solution., extracted with AcOEt. The organic layer was washed with water and brine, dried over MgSO4, and evaporated. The residue was purified by column chromatography on silica eluting with CH2Cl2 and methanol=from 98:2 to 95:5. The combined product fractions were evaporated to dryness to yield 33 mg (6%) of the title compound. MS (m/e): 357.1 (MH+).

Workup

  1. additionwas added at room temperature
  2. stirringstirred at 100° C. for 24 h
  3. extraction, extracted with AcOEt
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customThe residue was purified by column chromatography on silica eluting with CH2Cl2 and methanol=from 98:2 to 95:5
  8. customThe combined product fractions were evaporated to dryness

Sources & evidence

ORD record
ord-3bdd9f35a05b44de841ae1e5683be28a
Source dataset
uspto-grants-2009_06
Patent number
US07544683B2

Reaction notes

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