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

HRID 603069

Reaktionsgleichung

Reaktionsgleichung von HRID 603069
[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

Komponenten

10

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418903HCID 178418903, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel3×HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
200 °C

Versuchsvorschrift

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 dichlorobis(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+].

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-a6b36b5dbfb74f8583da127a9cd98ef6
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07906648B2

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