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

HRID 2190571Notes

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]([I:15])=[C:11]([Cl: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]([I:15])=[C:11]([Cl:16])[CH:10]=3)=[CH:4][N:3]=2)[CH2:20][CH2:21]1)=[O:24])[CH3:27]

Participants

Conditions

Temperature: 95 °C

Procedure

A solution of 6-Chloro-N-(3-chloro-4-iodo-phenyl)-nicotinamide (100 mg, 0.26 mmol), ethyl isonipecotate (60 mg, 0.38 mmol), diisopropyl ethyl amine (0.14 mL, 0.77 mmol) and a catalytic amount of DMAP in dioxane, in a sealed tube was heated at 85° C. for 19 h. Followed addition of another portion of ethyl isonipecotate (60 mg, 0.38 mmol) and the mixture was heated at 95° C. for 24 h. The mixture was then cooled, the solvent was evaporated and the residue was purified with a silica gel column and 20-40% EtOAc in hexanes to afford the product. HRMS m/z calcd for C20H21N3O3ClI [M+H]+: 514.0389. Found: 514.0387.

Workup

temperatureThe mixture was then cooled
customthe solvent was evaporated
customthe residue was purified with a silica gel column and 20-40% EtOAc in hexanes
customto afford the product

Sources & evidence

ORD record: ord-3a33481d38fc4cdbb3cdfe88d9e021e4
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08324385B2

Reaction notes

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