Cesium carbonate → HCID 118272053, compound

HRID 590876Notes

Reaction equation

[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH3:10])[N:5]=[C:4](Cl)[CH:3]=1.[C:12]1([C@H:18]([NH:20][C:21]([NH2:23])=[O:22])[CH3:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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.O1CCCC1>[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH3:10])[N:5]=[C:4]([NH:23][C:21]([NH:20][C@@H:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH3:19])=[O:22])[CH:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A flask was charged with 4,6-dichloro-2-methylnicotinonitrile (1500 mg), (R)-1-(1-phenylethyl)urea (1449 mg), xantphos (371 mg), palladium(II)acetate (90 mg) and cesium carbonate (5.23 g). Tetrahydrofuran (53 mL) was injected and the reaction was heated to 50° C. for 3 hours. LC/MS showed that the reaction cleanly proceeded to completion. The reaction mixture was filtered through celite and the filtrate was concentrated and purified by silica gel chromatography (0-30% DCM/EtOAc). (R) -1-(4-chloro-5-cyano-6-methylpyridin-2-yl)-3-(1-phenylethyl)urea (2.19 g, 87%) was isolated as an off-white solid. MS ESI calc'd for C16H15ClN4O [M+H]+ 315. found 315.

Workup

customLC/MS showed that the reaction
filtrationThe reaction mixture was filtered through celite
concentrationthe filtrate was concentrated
custompurified by silica gel chromatography (0-30% DCM/EtOAc)

Sources & evidence

ORD record: ord-58abdd4368e04998993ea62347bb5193
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09233979B2

Reaction notes

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