Ethyl 4-piperidinecarboxylate → 5'-(3-iodo-4-methyl-phenylcarbamoyl)-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-4 carboxylic acid ethyl ester

HRID 2190573Notes

Reaction equation

HRID 2190573 reaction equation
Cl[C:2]1[CH:18]=[CH:17][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([I:16])[CH:10]=2)=[O:7])=[CH:4][N:3]=1.[NH:19]1[CH2:29][CH2:28][CH:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:21][CH2:20]1.C(N(C(C)C)CC)(C)C>CN(C1C=CN=CC=1)C.O1CCOCC1>[CH2:26]([O:25][C:23]([CH:22]1[CH2:28][CH2:29][N:19]([C:2]2[CH:18]=[CH:17][C:5]([C:6](=[O:7])[NH:8][C:9]3[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([I:16])[CH:10]=3)=[CH:4][N:3]=2)[CH2:20][CH2:21]1)=[O:24])[CH3:27]

Participants

6

Reactant 3

HCID 70770Ethyl 4-piperidinecarboxylateHCID 81531DiisopropylethylamineHCID 79255626-chloro-N-(3-iodo-4-methyl-phenyl)-nicotinamide

Product 1

HCID 593180575'-(3-iodo-4-methyl-phenylcarbamoyl)-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-4 carboxylic acid ethyl esterYield 75.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 6-chloro-N-(3-iodo-4-methyl-phenyl)-nicotinamide (360 mg, 0.97 mmol), ethyl isonipecotate (460 mg, 2.91 mmol), diisopropylethyl amine (0.51 mL, 2.91 mmol) and a catalytic amount of DMAP in dioxane (15 mL) was heated at 120° C. in a sealed tube until consumption of the limiting reagent, as judged by TLC. The reaction mixture was then cooled and partitioned between EtOAc and water. The organic layer was then dried over Na2SO4, filtered and concentrated. The residue was purified with a silica gel column and 0-50% EtOAc in hexanes gradient to afford the product (360 mg, Yield 75%). HRMS m/z calcd for C21H24N3O3I [M+H]+: 494.0935. Found: 494.0935.

Workup

  1. temperatureThe reaction mixture was then cooled
  2. custompartitioned between EtOAc and water
  3. dry with materialThe organic layer was then dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified with a silica gel column and 0-50% EtOAc in hexanes gradient

Sources & evidence

ORD record
ord-f4386fc00cd24d06808cda684f120170
Source dataset
uspto-grants-2012_12
Patent number
US08324385B2

Reaction notes

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