Piperidine → HCID 59730288, compound

HRID 130716Notes

Reaction equation

HRID 130716 reaction equation
O[CH2:2][CH2:3][C:4]1[CH:19]=[CH:18][C:7]([O:8][C:9]2[CH:17]=[CH:16][C:12]([C:13]([NH2:15])=[O:14])=[CH:11][N:10]=2)=[CH:6][CH:5]=1.CCN(CC)CC.CS(Cl)(=O)=O.[NH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1>CN(C=O)C.O>[N:32]1([CH2:2][CH2:3][C:4]2[CH:19]=[CH:18][C:7]([O:8][C:9]3[CH:17]=[CH:16][C:12]([C:13]([NH2:15])=[O:14])=[CH:11][N:10]=3)=[CH:6][CH:5]=2)[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

7

Reactant 4

HCID 8082PiperidineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59730077HCID 59730077, compound

Product 1

HCID 59730288HCID 59730288, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Dissolve 6-[4-(2-hydroxy-ethyl)-phenoxy]-nicotinamide (100 mg, 0.38 mmol) under N2 atmosphere in dry DMF (4 mL). Add Et3N (108 μL, 0.77 mmol) then cool the mixture at 0° C., add MsCl (29 μL, 0.38 mmol), allow the mixture to warm to room temperature. After 1 hour add piperidine (76 μL, 0.77 mmol) and heat the mixture at 90° C. for 1 hour. Cool to ambient temperature and pour into water. Extract the aqueous layer with EtOAc. Dry the organic layer over MgSO4. Eliminate the solvent. Purify by flash chromatography on silica gel (eluent: CHCl3/5% EtOH/0.5% NH4OH) to give the title compound (65 mg, 55%). Electrospray MS M+1 ion=326, 1H-NMR (CDCl3, 400 MHz): 8.58 (d, 1H, J=2.4 Hz), 8.14 (dd, 1H, J=2.4 and 8.5 Hz), 7.25-7.23 (m, 2H), 7.07-7.03 (m, 2H), 6.93 (d, 1H, J=8.5 Hz), 6.12 (bs, 2H), 2.88-2.80 (m, 2H), 2.68-2.65 (m, 2H), 2.53-2.44 (m, 4H), 1.67-1.59 (m, 4H), 1.51-1.43 (m, 2H).

Workup

  1. temperatureheat the mixture at 90° C. for 1 hour
  2. temperatureCool to ambient temperature
  3. extractionExtract the aqueous layer with EtOAc
  4. dry with materialDry the organic layer over MgSO4
  5. customPurify by flash chromatography on silica gel (eluent: CHCl3/5% EtOH/0.5% NH4OH)

Sources & evidence

ORD record
ord-bc1fd6aa52d240e39149056fa39b0114
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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