Sodium hydride → HCID 178510093, compound

HRID 1984022Notes

Reaction equation

HRID 1984022 reaction equation
[CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11]([C@H:13]3[CH2:18][CH2:17][C@H:16]([OH:19])[CH2:15][CH2:14]3)=[O:12])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Cl[C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][N:24]=1.C([O-])(O)=O.[Na+]>CN(C)C(=O)C>[CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11]([C@H:13]3[CH2:18][CH2:17][C@H:16]([O:19][C:23]4[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][N:24]=4)[CH2:15][CH2:14]3)=[O:12])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 178520990HCID 178520990, compound2×

Product 1

HCID 178510093HCID 178510093, compoundYield 18.9%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a mixture of 115 mg (0.43 mmol) of trans-(4-Cyclobutyl-piperazin-1-yl)-(4-hydroxy-cyclohexyl)-methanone (Intermediate 3) in 1 ml of N,N-dimethylacetamide (DMA), 19 mg (0.44 mmol) of sodium hydride was added at room temperature and stirred for 30 min. To the mixture, 100 mg (0.72 mmol) of 6-chloronicotinonitrile (commercially available) was added and stirred at 160° C. for 14 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 30 mg (11%) of the title compound. MS (m/e): 369.2 (MH+).

Workup

  1. additionwas added at room temperature
  2. stirringstirred at 160° C. for 14 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-4e3cf94dd54648f0957a430718ab7343
Source dataset
uspto-grants-2009_06
Patent number
US07544683B2

Reaction notes

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