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

HRID 901537노트

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HRID 901537 반응식
[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

참가 물질

10

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 178418903HCID 178418903, 화합물촉매HCID 702Ethanol용매HCID 962Water용매3회HCID 6342Acetonitrile용매

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온도
200 °C

실험 절차

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+].

후처리

  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

출처 및 근거

ORD 기록
ord-fa87b4a5e9864950a9212dc17122dd7f
출처 데이터셋
uspto-grants-2008_04
특허 번호
US07361764B2

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