3-Aminopyridine → 4-(Pyridin-3-ylamino)picolinonitrile

HRID 1908977Notes

Reaction equation

HRID 1908977 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]#[N:9])[CH:3]=1.[NH2:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[N:13]1[CH:14]=[CH:15][CH:16]=[C:11]([NH:10][C:2]2[CH:7]=[CH:6][N:5]=[C:4]([C:8]#[N:9])[CH:3]=2)[CH:12]=1

Participants

7

Reactant 4

HCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 6933424-Chloro-2-pyridinecarbonitrile

Product 1

HCID 552106954-(Pyridin-3-ylamino)picolinonitrileYield 100%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

4-Chloro-2-pyridinecarbonitrile (1 g, 7 mmol, 1 eq), 3-aminopyridine (0.815 mg, 8.66 mmol, 1.20 eq), Cs2CO3 (3.29 g, 10.1 mmol, 1.40 eq), Pd2(dba)3 (332 mg, 0.577 mmol, 0.0800 eq), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (501 mg, 0.866 mmol, 0.120 eq) and dioxane (18 mL) were added to a microwave vial. The vial was purged with argon, capped and heated at 100° C. for 18 h. After cooling the reaction was filtered over a plug of celite and the plug was washed with 5% MeOH/CH2Cl2. The solvents were removed in vacuo and the crude mixture was purified by flash chromatography on silica gel afforded 1.374 g (97%) of the title compound as an orange solid: 1H NMR (400 MHz, CDCl3) δ1H NMR (400 MHz, DMSO-d6) δ 9.42 (s, 1H), 8.49 (d, J=2.6 Hz, 1H), 8.34-8.31 (m, 2H), 7.73 (dq, J=1.3, 8.2 Hz, 1H), 7.43-7.40 (m, 1H), 7.39 (d, J=2.3 Hz, 1H), 7.13 (dd, J=2.4, 5.9 Hz, 1H); ES-MS [M+1]+:197.1.

Workup

  1. customThe vial was purged with argon
  2. customcapped
  3. temperatureAfter cooling the reaction
  4. filtrationwas filtered over a plug of celite
  5. washthe plug was washed with 5% MeOH/CH2Cl2
  6. customThe solvents were removed in vacuo
  7. customthe crude mixture was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-0c867ae1f748496ba640f480be164d3c
Source dataset
uspto-grants-2013_12
Patent number
US08598345B2

Reaction notes

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