1-Cyclohexenylboronic acid → 4-[5-Amino-6-(1-cyclohexen-1-yl)-2-pyridinyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester

HRID 1992016Notes

Reaction equation

HRID 1992016 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[C:16](Br)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:22]1(B(O)O)[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]=1>CCO.C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+].CCOCC.[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[C:16]([C:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]=3)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 2

HCID 38629021-Cyclohexenylboronic acidHCID 591286051,1-Dimethylethyl 4-(5-amino-6-bromo-2-pyridinyl)-1-piperidinecarboxylate

Product 1

HCID 591285794-[5-Amino-6-(1-cyclohexen-1-yl)-2-pyridinyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl esterYield 74.6%

Reagents, catalysts & solvents 6

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 10340Sodium CarbonateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 5-amino-6-bromo-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (331 mg, 0.93 mmol) (as prepared in Example 54, step (c)) and cyclohexen-1-yl boronic acid (141 mg, 1.11 mmol) in 5 mL of EtOH, 10 mL of toluene and 5 mL of 2 M Na2CO3, was added Pd(PPh3)4 (107 mg, 0.0930 mmol) and the result was heated at 80° C. for 16 h. The reaction was diluted with 100 mL of ether and 100 mL of brine and the layers were separated. The organic layer was dried (Na2SO4) and concentrated in vacuo. Purification of the residue by column chromatography (silica gel, 30-60% ether-hexanes) afforded 248 mg (74%) the title compound as an light brown oil LC-MS (ESI, m/z): Calcd. for C21H32N3O2 (M+H), 358.2, found 358.1.

Workup

  1. customthe layers were separated
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customPurification of the residue by column chromatography (silica gel, 30-60% ether-hexanes)

Sources & evidence

ORD record
ord-485fc48cfbaf4da7aa7a6a990d3c07f5
Source dataset
uspto-grants-2010_01
Patent number
US07645755B2

Reaction notes

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