Cesium carbonate → N-[4-(3-fluoro-4-nitro-anilino)-2-pyridyl]cyclopropanecarboxamide

HRID 2200113Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]([CH:11]2[CH2:13][CH2:12]2)=[O:10])[CH:3]=1.[F:14][C:15]1[CH:16]=[C:17]([CH:19]=[CH:20][C:21]=1[N+:22]([O-:24])=[O:23])[NH2:18].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C([O-])([O-])=O.[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[F:14][C:15]1[CH:16]=[C:17]([CH:19]=[CH:20][C:21]=1[N+:22]([O-:24])=[O:23])[NH:18][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]([CH:11]2[CH2:13][CH2:12]2)=[O:10])[CH:3]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Under N2, mix N-(4-bromo-2-pyridyl)cyclopropanecarboxamide (460 mg, 1.9 mmol), 3-fluoro-4-nitroaniline (359 mg, 2.3 mmol), palladium(II) acetate [Pd(OAc)2, 43.2 mg, 0.19 mmol], 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-Phos, 158 mg, 0.38 mmol), Cs2CO3 (1.2 g, 3.8 mmol) and anhydrous toluene (10 mL). Stir the mixture at 120° C. under N2 for 16 hrs. Cool to room temperature, pour the reaction mixture to water (50 mL), extract with EtOAc (15 mL×3), combine the organic layers and dry over anhydrous Na2SO4. Concentrate under reduced pressure to give the crude product. Purification by chromatography (silica gel, PE:EtOAc=54:46) affords the target compound (160 mg, 22%). MS: (M+1): 317.2.

Workup

temperatureCool to room temperature
extractionextract with EtOAc (15 mL×3)
dry with materialdry over anhydrous Na2SO4
concentrationConcentrate under reduced pressure
customto give the crude product
customPurification by chromatography (silica gel, PE:EtOAc=54:46)

Sources & evidence

ORD record: ord-60cc8c41362e42cc85b949ed86333ad0
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09359338B2

Reaction notes

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