3-Aminopyridine → 5-[2-(Pyridin-3-ylamino)-pyrimidin-4-yl]-thiophene-2-carboxylic acid ethyl ester

HRID 1012185Notes

Reaction equation

CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[K+].[K+].[CH2:49]([O:51][C:52]([C:54]1[S:55][C:56]([C:59]2[CH:64]=[CH:63][N:62]=[C:61](Cl)[N:60]=2)=[CH:57][CH:58]=1)=[O:53])[CH3:50].[NH2:66][C:67]1[CH:68]=[N:69][CH:70]=[CH:71][CH:72]=1>O1CCOCC1.CCOC(C)=O.O.CC(O)=O.CC(O)=O.[Pd]>[CH2:49]([O:51][C:52]([C:54]1[S:55][C:56]([C:59]2[CH:64]=[CH:63][N:62]=[C:61]([NH:66][C:67]3[CH:68]=[N:69][CH:70]=[CH:71][CH:72]=3)[N:60]=2)=[CH:57][CH:58]=1)=[O:53])[CH3:50]

Participants

Conditions

Temperature: 100 °C

Procedure

Palladium II acetate (8.3 mg, 0.1 mmol) and xantphos 42.8 mg, 0.2 mmol) were precombined in 4 mL dry dioxane under nitrogen gas. Potassium carbonate (1.03 g, 7.46 mmol) was added followed by a solution of 5-(2-Chloro-pyrimidin-4-yl)-thiophene-2-carboxylic acid ethyl ester (100 mg, 0.373 mmol) and 3-aminopyridine (42 mg, 0.447 mmol) in 3 mL dioxane. The reaction was heated in a capped vial at 100° C. for 20 h. The cooled reaction mixture was diluted with EtOAc and water and the layers were separated. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was redissolved in ethyl ether and treated with 2 M HCl in ether to generate a precipitate which was collected by filtration to afford 76 mg (56.3%) of the title compound. The crude material was used in the next step.

Workup

customThe cooled reaction mixture
customthe layers were separated
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated in vacuo
dissolutionThe residue was redissolved in ethyl ether
additiontreated with 2 M HCl in ether
filtrationwas collected by filtration

Sources & evidence

ORD record: ord-dc23e332563f4fb4bbb05c3fd47ca62e
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977481B2

Reaction notes

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