Diisopropylethylamine → 4-Hydroxy-4-phenyl-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-5'-carboxylic acid (3-iodo-4-methyl-phenyl)-amide

HRID 2190562Notes

Reaction equation

HRID 2190562 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.C(N(C(C)C)CC)(C)C.[OH:28][C:29]1([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1>CN(C1C=CN=CC=1)C.O1CCOCC1>[I:16][C:11]1[CH:10]=[C:9]([NH:8][C:6]([C:5]2[CH:17]=[CH:18][C:2]([N:32]3[CH2:33][CH2:34][C:29]([OH:28])([C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[CH2:30][CH2:31]3)=[N:3][CH:4]=2)=[O:7])[CH:14]=[CH:13][C:12]=1[CH3:15]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 963874-Phenylpiperidin-4-olHCID 79255626-chloro-N-(3-iodo-4-methyl-phenyl)-nicotinamide

Product 1

HCID 593180914-Hydroxy-4-phenyl-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-5'-carboxylic acid (3-iodo-4-methyl-phenyl)-amideYield 65%

Reagents, catalysts & solvents 2

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

Procedure

A solution of 6-chloro-N-(3-iodo-4-methyl-phenyl)-nicotinamide (100 mg, 0.26 mmol), a catalytic amount of DMAP, diisopropylethyl amine (0.14 mL, 8.1 mmol), 4-hydroxy-4-phenyl piperidine (140 mg, 8.1 mmol) in 5 mL in dioxane was heated at 95° C. in a sealed tube for about 48 h. The reaction mixture was then cooled and partitioned between EtOAc and aq. saturated Na2CO3. The organic layer was then collected, dried over Na2SO4 filtered and concentrated. The residue was chromatographed with a silica gel column and 20-100% EtOAc in hexanes to afford the product (90 mg. Yield: 65%). HRMS m/z calcd for C24H24N3O2I [M+H]+: 514.0986. Found: 514.0987.

Workup

  1. temperatureThe reaction mixture was then cooled
  2. custompartitioned between EtOAc and aq. saturated Na2CO3
  3. customThe organic layer was then collected
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed with a silica gel column and 20-100% EtOAc in hexanes
  8. customto afford the product (90 mg. Yield: 65%)

Sources & evidence

ORD record
ord-ca50cbd9d39047a985c9d4a5ef448b53
Source dataset
uspto-grants-2012_12
Patent number
US08324385B2

Reaction notes

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