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

HRID 729846

反応式

HRID 729846 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.[Cl-].[NH4+].C([N:22](CC)CC)C.[CH3:27][O:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][C:34]=1[O:35][CH3:36].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.O.Cl[Pd-2](Cl)(P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(#N)C>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:11]=[N:12][C:13]([NH2:22])=[CH:14][CH:15]=2)=[O:9])=[CH:6][C:5]([C:32]2[CH:31]=[CH:30][C:29]([O:28][CH3:27])=[C:34]([O:35][CH3:36])[CH:33]=2)=[CH:4][N:3]=1

参加物

10

反応物 5

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 25517Ammonium ChlorideHCID 27347023,4-Dimethoxyphenylboronic acidHCID 59699837(2-Amino-5-bromo-pyridin-3-yl)-(6-fluoro-pyridin-3-yl)methanone

生成物 1

HCID 59699897[2-Amino-5-(3,4-dimethoxy-phenyl)-pyridin-3-yl]-(6-amino-pyridin-3-yl)-methanone収率 31%

試薬・触媒・溶媒 4

HCID 178418903HCID 178418903、化合物触媒HCID 702Ethanol溶媒HCID 962Water溶媒3 回HCID 6342Acetonitrile溶媒

反応条件

温度
200 °C

実験手順

A solution of (2-amino-5-bromo-pyridin-3-yl)-(6-fluoro-pyridin-3-yl)-methanone (120 mg, 0.405 mmol), ammonium chloride (5 equiv.), and triethyl amine (5 eq.) in absolute ethanol (0.2 M) was sealed in a Smith process vial. The reaction was heated in a Personal Chemistry® microwave reactor to 200° C. for 25 minutes. The mixture was diluted with water, and the resulting yellow precipitate was filtered off, washed with water, and dried in vacuo. The crude product was mixed with 3,4-dimethoxyphenyl boronic acid (1.3 equiv.), 6 mol % of dichlorbis(triphenylphosphino) palladium (II) and a 3:2:1 mixture of acetonitrile, water, and a 2 M aqueous solution of sodium carbonate (0.11 M). The reaction was run in a Personal Chemistry® microwave reactor at 165° C. for 1200 s. Water was added and the mixture was extracted three times with ethyl acetate. Purification was accomplished by flash chromatography on silica gel with a gradient of ethyl acetate/hexanes and afforded [2-amino-5-(3,4-dimethoxy-phenyl)-pyridin-3-yl]-(6-amino-pyridin-3-yl)-methanone as a yellow solid (37 mg, 31% yield). 1H NMR (DMSO-d6): δ 8.50 (d, J=2.5 Hz, 1H), 8.29 (d, J=2.0 Hz, 1H), 7.86 (d, J=2.0 Hz, 1H), 7.75 (dd, J=2.0, 8.5 Hz, 1H), 7.15 (d, J=2.0 Hz, 1H), 7.06 (m, 3H), 6.98 (d, J=8.0 Hz, 1H), 6.92 (broad s, 2H), 6.50 (d, J=9.0 Hz, 1H), 3.80 (s, 3H), 3.75 (s, 3H). HPLC/MS m/z: 351 [MH+].

後処理

  1. filtrationthe resulting yellow precipitate was filtered off
  2. washwashed with water
  3. customdried in vacuo
  4. extractionthe mixture was extracted three times with ethyl acetate
  5. customPurification

出典と根拠

ORDレコード
ord-c3dccfd7e4154314bb228178ccf1905b
出典データセット
uspto-grants-2009_09
特許番号
US07582637B2

関連ノート

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