2-Chloropyridine-4-carbonyl chloride → 2-Chloro-N-[4-(3-furyl)-5-(tetrahydropyran-4-ylcarbonyl)thiazol-2-yl]pyridine-4-carboxamide

HRID 337520Notes

Reaction equation

[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([C:9]2[S:13][C:12]([NH2:14])=[N:11][C:10]=2[C:15]2[CH:19]=[CH:18][O:17][CH:16]=2)=[O:8])[CH2:3][CH2:2]1.[Cl:20][C:21]1[N:22]=[CH:23][CH:24]=[C:25]([CH:29]=1)[C:26](Cl)=[O:27]>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[Cl:20][C:21]1[CH:29]=[C:25]([C:26]([NH:14][C:12]2[S:13][C:9]([C:7]([CH:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)=[O:8])=[C:10]([C:15]3[CH:19]=[CH:18][O:17][CH:16]=3)[N:11]=2)=[O:27])[CH:24]=[CH:23][N:22]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Compound 610 (100 mg, 0.359 mmol) was dissolved in pyridine (3 mL), and 6-chloroisonicotinoyl chloride (560 mg, 3.18 mmol) and DMAP (4.40 mg, 0.0360 mmol) were added thereto, followed by stirring at 80° C. for 3 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was poured into a saturated aqueous solution of sodium hydrogencarbonate, and the precipitated solid was collected by filtration. The resulting solid was purified through silica gel column chromatography (hexane:ethyl acetate=3:1), followed by recrystallizing from a mixed solvent of ethanol and water to afford the entitled Compound 616 (54.5 mg, 36%) as a white solid.

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
additionthe resulting residue was poured into a saturated aqueous solution of sodium hydrogencarbonate
filtrationthe precipitated solid was collected by filtration
customThe resulting solid was purified through silica gel column chromatography (hexane:ethyl acetate=3:1)
customby recrystallizing from a mixed solvent of ethanol and water

Sources & evidence

ORD record: ord-f43e6ebf61fe4321a040068318638694
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889718B2

Reaction notes

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