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

HRID 603069

Reaction equation

HRID 603069 reaction equation
[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

Participants

10

Reactant 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

Product 1

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

Reagents, catalysts & solvents 4

HCID 178418903HCID 178418903, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent3×HCID 6342AcetonitrileSolvent

Conditions

Temperature
200 °C

Procedure

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+].

Workup

  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

Sources & evidence

ORD record
ord-a6b36b5dbfb74f8583da127a9cd98ef6
Source dataset
uspto-grants-2011_03
Patent number
US07906648B2

Linked notes

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