HCID 22251100, compound → HCID 22251152, compound

HRID 890511Notes

Reaction equation

HRID 890511 reaction equation
[N:1]([CH2:4][C:5]([N:7]([CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:6])=[N+]=[N-]>CO.[Pd]>[NH2:1][CH2:4][C:5]([N:7]([CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:6]

Participants

4

Reactant 1

HCID 22251100HCID 22251100, compound

Product 1

HCID 22251152HCID 22251152, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of 2-chloro-N-cyclohexyl-N-phenylacetamide (503 mg, 2.0 mmol) in acetone (30 mL) was added sodium iodide (800 mg, 5.6 mmol). The reaction mixture was heated at reflux for 4 hours before it was cooled to room temperature. The solid material was filtered off, and the solvent removed from the filtrate under reduced pressure, to afford 2-iodo-N-cyclohexyl-N-phenylacetamide, which was subjected to subsequent reactions without further purification. B. To a solution of 2-iodo-N-cyclohexyl-N-phenylacetamide (obtained from A. above) in anhydrous DMF (30 mL) was added sodium azide (325 mg, 5.0 mmol), and the contents were heated at 80° C. for 10 hours. The reaction mixture was filtered, the solids washed with acetone (2×5 mL), and the solvent removed from the filtrate under reduced pressure, to afford 2-azido-N-cyclohexyl-N-phenylacetamide. C. To a solution of 2-azido-N-cyclohexyl-N-phenylacetamide (obtained from B. above) dissolved in methanol (50 mL) was added 10% Pd/C (90 mg, 0.09 mmol), and the reaction suspension was hydrogenated at room temperature under hydrogen (50 psi) for 5 hours. After filtration and concentration, the crude product was purified on silica gel using a methanol/dichloromethane gradient (0% to 10% methanol) to furnish 2-amino-N-cyclohexyl-N-phenylacetamide (320 mg, 69% yield). D. To a solution of exo-2-chloro-syn-7-hydroxymethyl-5-oxo-bicyclo[2.2.1]heptane (35 mg, 0.20 mmol) in 1-butanol (6 mL) was added 2-amino-N-cyclohexyl-N-phenylacetamide (46 mg, 0.20 mmol) and triethylamine (50 μL, 0.36 mmol). The reaction mixture was stirred at 100° C. for 2 days, then cooled to room temperature, concentrated under reduced pressure, and the residue purified on silica gel (10% methanol/dichloromethane) to afford N-cyclohexyl-2-{[7-(hydroxymethyl)-5-oxobicyclo[2.2.1]hept-2-yl]amino}-N-phenylacetamide CVT-6440 (8 mg, 10% yield). (M+1)=371.15. B. Preparation of a Compound of Formula I in which X is —N— and Z is —C(O)—

Workup

  1. filtrationAfter filtration and concentration
  2. customthe crude product was purified on silica gel using a methanol/dichloromethane gradient (0% to 10% methanol)

Sources & evidence

ORD record
ord-6a52d12520a243369e6dd0fb8ee4aaa5
Source dataset
uspto-grants-2006_02
Patent number
US06995285B2

Reaction notes

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