Triethylamine → HCID 86617023, compound

HRID 734362Notes

Reaction equation

HRID 734362 reaction equation
[Cl:1][C:2]1[N:9]=[C:8](Cl)[CH:7]=[C:6]([CH:11]([F:13])[F:12])[C:3]=1[C:4]#[N:5].C([N:16]([CH2:19][CH3:20])[CH2:17][CH3:18])C.[C:21]([N:28]1[CH2:33]CC(N)C[CH2:29]1)([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22]>C(O)C>[C:24]([O:23][C:21](=[O:22])[N:28]([CH:33]1[CH2:18][CH2:17][N:16]([C:8]2[CH:7]=[C:6]([CH:11]([F:13])[F:12])[C:3]([C:4]#[N:5])=[C:2]([Cl:1])[N:9]=2)[CH2:19][CH2:20]1)[CH3:29])([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 84819926HCID 84819926, compound

Product 1

HCID 86617023HCID 86617023, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of the above nicotinonitrile (2.4 g, 10.8 mmol) in ethanol (40 mL) was cooled in a dry ice/acetone bath. Triethylamine (1.5 mL, 11.0 mmol) and N-methyl, N-boc-4-aminopiperidine were added and the reaction mixture was allowed to warm gradually to room temperature overnight. The reaction was concentrated, taken up in ethyl acetate (200 mL) and washed with 1 N HCl (2×100 mL). The organic phase was dried (magnesium sulfate) and concentrated to provide a 4 to 1 mixture of addition products to the 6 and 2 position, respectively. These regioisomers were separated by silica gel chromatography using a gradient of ethyl acetate in hexanes as the mobile phase to provide 1.3 g (30%) of (6′-chloro-5′-cyano-4′-difluoromethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-methyl-carbamic acid tert-butyl ester as a white solid.

Workup

  1. concentrationThe reaction was concentrated
  2. washwashed with 1 N HCl (2×100 mL)
  3. dry with materialThe organic phase was dried (magnesium sulfate)
  4. concentrationconcentrated
  5. customto provide a 4
  6. additionto 1 mixture of addition products to the 6 and 2 position
  7. customThese regioisomers were separated by silica gel chromatography

Sources & evidence

ORD record
ord-af90dadac0f34ef899acc41cfe83ad80
Source dataset
uspto-grants-2009_09
Patent number
US07592353B2

Reaction notes

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