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

HRID 1043345
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HRID 1043345 반응식
[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]
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참가 물질

9

반응물 2

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

생성물 1

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

시약·촉매·용매 6

HCID 178418397HCID 178418397, 화합물촉매
HCID 702
Ethanol
용매
HCID 1140Toluene용매
HCID 3283Diethyl Ether용매
HCID 10340Sodium Carbonate용매
HCID 57417360Sodium chloride; water용매

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온도
80 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-32e2d261308f448fa59d6e1c4aa1d70e
출처 데이터셋
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08557847B2

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