Cesium carbonate → 1-(4-Cyano-pyridin-2-yl)-3-methyl-urea

HRID 602419Notes

Reaction equation

Cl[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][N:9]=1)[C:5]#[N:6].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:16][NH:17][C:18]([NH2:20])=[O:19]>O1CCOCC1.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].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:5]([C:4]1[CH:7]=[CH:8][N:9]=[C:2]([NH:20][C:18]([NH:17][CH3:16])=[O:19])[CH:3]=1)#[N:6]

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 2-chloro-isonicotinonitrile [Talik et al. Rocz. Chem.; 29; 1955; 1019, 1025.] (13.9 g, 0.1 mol), Pd2 dba3 (2.0 g, 2 mmol), Xantphos (3.6 g, 6.22 mmol), cesium carbonate (39.1 g, 120 mmol) and methylurea (37.04 g, 0.5 mol) in dioxane (800 mL), under a nitrogen atmosphere was heated for 8 hours at 130° C. (bath temperature). On cooling the reaction mixture was concentrated in vacuo. The residue was partitioned between CH2Cl2 and water. The organic phase was washed with brine, dried, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel (gradient elution: 100% hexane to 100% EtOAc) to give 1-(4-cyano-pyridin-2-yl)-3-methyl-urea (12.1 g) as a solid; Mp. 203-204° C.

Workup

temperatureOn cooling the reaction mixture
concentrationwas concentrated in vacuo
customThe residue was partitioned between CH2Cl2 and water
washThe organic phase was washed with brine
customdried
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by chromatography on silica gel (gradient elution: 100% hexane to 100% EtOAc)

Sources & evidence

ORD record: ord-fc970403f7024bdca8805fe7be8a77bf
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07906533B2

Reaction notes

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