Isobutylamine → [2-Amino-5-(3,4-dimethoxy-phenyl)-pyridin-3-yl]-(6-isobutylamino-pyridin-3-yl)-methanone

HRID 603073

反応式

HRID 603073 の反応式
[NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:11]=[N:12][C:13](F)=[CH:14][CH:15]=2)=[O:9])=[CH:6][C:5](Br)=[CH:4][N:3]=1.[CH2:18]([NH2:22])[CH:19]([CH3:21])[CH3:20].[CH3:23][O:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][C:30]=1[O:31][CH3:32].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.[Pd+2].O.C(#N)C.C(N(CC)CC)C>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:11]=[N:12][C:13]([NH:22][CH2:18][CH:19]([CH3:21])[CH3:20])=[CH:14][CH:15]=2)=[O:9])=[CH:6][C:5]([C:28]2[CH:27]=[CH:26][C:25]([O:24][CH3:23])=[C:30]([O:31][CH3:32])[CH:29]=2)=[CH:4][N:3]=1

参加物

10

反応物 4

HCID 6558IsobutylamineHCID 10340Sodium CarbonateHCID 27347023,4-Dimethoxyphenylboronic acidHCID 59699837(2-Amino-5-bromo-pyridin-3-yl)-(6-fluoro-pyridin-3-yl)methanone

生成物 1

HCID 59699987[2-Amino-5-(3,4-dimethoxy-phenyl)-pyridin-3-yl]-(6-isobutylamino-pyridin-3-yl)-methanone収率 71%

試薬・触媒・溶媒 5

HCID 105144Allyl(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)chloropalladium(II)触媒HCID 702Ethanol溶媒HCID 962Water溶媒2 回HCID 6342Acetonitrile溶媒HCID 8471Triethylamine溶媒

実験手順

A solution of (2-amino-5-bromo-pyridin-3-yl)-(6-fluoro-pyridin-3-yl)-methanone, 1.1 equivalents of isobutylamine and 1.2 equivalents (or 2.3 equivalents for amines in salt form) of triethyl amine are dissolved in absolute ethanol (overall concentration of the starting material: 0.22 M) and sealed in a Smith process vial. The reaction was run in a Personal Chemistry® microwave, reactor at 150° C. for 900 s. The solvent was evaporated and the crude mixed with 1.3 equivalents of 3,4-dimethoxyphenylboronic acid, 6 mol % of dichlorobis (triphenylphosphinol) palladium (II) and a 3:2:1 mixture of acetonitrile, water, and an aqueous 2 M solution of sodium carbonate (overall concentration of starting material: 0.18 m). The reaction was run in a Personal Chemistry® microwave reactor at 165° C. for 1200 s. Water was added and the mixture extracted three times with ethyl acetate Purification by flash chromatography on silica gel with a gradient of ethyl acetate/hexane to afforded [2-Amino-5-(3,4-dimethoxy-phenyl)-pyridin-3-yl]-(6-isobutylamino-pyridin-3-yl)-methanone as a yellow solid (71% yield). 1H NMR (DMSO-d6): δ 8.49 (d, J=2.0 Hz, 1H), 8.32 (d, J=2.5 Hz, 1H), 7.86 (d, J=3.0 Hz, 1H), 7.72 (d, J=9.0 Hz, 1H), 7.57 (broad s, 1H), 7.14 (d, J=2.0 Hz, 1H), 7.06 (dd, J=2.0, 8.5 Hz, 1H), 7.03 (broads, 2H), 6.98 (d, J=8.0 Hz, 1H), 6.56 (d, J=8.5 Hz, 1H), 3.79 (s, 3H), 3.75 (s, 3H), 3.15 (broad s, 2H), 1.83 (m, 1H), 0.89 (d, J=6.5 Hz, 6H); HPLC/MS m/z: 407.2 [MH]+.

後処理

  1. concentrationoverall concentration of the starting material
  2. custom0.22 M) and sealed in a Smith process vial
  3. customThe solvent was evaporated
  4. waitThe reaction was run in a Personal Chemistry® microwave reactor at 165° C. for 1200 s
  5. extractionthe mixture extracted three times
  6. customwith ethyl acetate Purification by flash chromatography on silica gel with a gradient of ethyl acetate/hexane

出典と根拠

ORDレコード
ord-dac5ba14da884c548832485d94b4e903
出典データセット
uspto-grants-2011_03
特許番号
US07906648B2

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