Potassium Carbonate → 2-{[6-(Morpholin-4-ylmethyl)pyridin-2-yl]amino}-5-pyridin-3-ylthiophene-3-carbonitrile

HRID 386135Notes

Reaction equation

[NH2:1][C:2]1[S:3][C:4]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[CH:5][C:6]=1[C:7]#[N:8].Br[C:16]1[N:21]=[C:20]([CH2:22][N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:19]=[CH:18][CH:17]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>C(O)(CC)(C)C>[N:23]1([CH2:22][C:20]2[N:21]=[C:16]([NH:1][C:2]3[S:3][C:4]([C:9]4[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=4)=[CH:5][C:6]=3[C:7]#[N:8])[CH:17]=[CH:18][CH:19]=2)[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1

Participants

Conditions

Temperature: 100 °C

Procedure

2-Amino-5-pyridin-3-ylthiophene-3-carbonitrile (76 mg, 0.38 mmol), 4-[(6-bromopyridin-2-yl)methyl]morpholine (Example 45, Step 1) (97 mg, 0.38 mmol), dibenyzlideneacetone bis(triphenylphosphine) (17.29 mg, 0.02 mmol), 2-dicylohexylphosphino-2′,4′,6′-triisopropyl-1,1-biphenyl (45.0 mg, 0.09 mmol), and potassium carbonate (57.4 mg, 0.42 mmol) were dissolved in tert-amyl alcohol (3.8 ml) and the mixture was bubbled with nitrogen for 5 min. The reaction was then heated to 100° C. overnight. The mixture was diluted with ethyl acetate and water and extracted with ethyl acetate (3×50 mL). The combined organics were washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with dichloromethane/methanol to afford the title compound as a solid.

Workup

customthe mixture was bubbled with nitrogen for 5 min
additionThe mixture was diluted with ethyl acetate and water
extractionextracted with ethyl acetate (3×50 mL)
washThe combined organics were washed with water and brine
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by column chromatography on silica gel
washeluting with dichloromethane/methanol

Sources & evidence

ORD record: ord-b933f44bc8504ab4ac58ca4d258c67f4
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367706B2

Reaction notes

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