Cesium carbonate → HCID 90355855, compound

HRID 1470331Notes

Reaction equation

[NH2:1][C:2]1[CH:9]=[C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@@H:12]2[NH2:17])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Cl[C:19]1[CH:24]=[C:23]([CH3:25])[CH:22]=[C:21]([CH3:26])[N:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:17][C@H:12]1[CH2:13][CH2:14][CH2:15][CH2:16][C@H:11]1[NH:10][C:8]1[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([NH:1][C:19]2[CH:24]=[C:23]([CH3:25])[CH:22]=[C:21]([CH3:26])[N:20]=2)[CH:9]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of rel-2-amino-4-{[(1R,2S)-2-aminocyclohexyl]amino}benzonitrile (100 mg, 0.430 mmol), 2-chloro-4,6-dimethylpyridine (65 mg, 0.46 mmol), palladium(II) acetate (12 mg, 0.053 mmol), cesium carbonate (284 mg, 0.860 mmol) and Xantphos (58 mg, 0.10 mmol) was purged with nitrogen. To this mixture was added 1,4-dioxane (10 mL), and the reaction mixture was heated to 90° C. under a nitrogen atmosphere. After 3 hours, the reaction mixture was cooled to ambient temperature and concentrated under reduced pressure. The residue was purified via reverse phase HPLC (acetonitrile/water with 0.1% TFA, linear gradient) to give rel-4-{[(1R,2S)-2-aminocyclohexyl]amino}-2-[(4,6-dimethylpyridin-2-yl)amino]benzonitrile. MS ESI calc'd. for C20H26N5 [M+H]+ 336. Found 336.

Workup

customwas purged with nitrogen
additionTo this mixture was added 1,4-dioxane (10 mL)
temperaturethe reaction mixture was cooled to ambient temperature
concentrationconcentrated under reduced pressure
customThe residue was purified via reverse phase HPLC (acetonitrile/water with 0.1% TFA, linear gradient)

Sources & evidence

ORD record: ord-13658aadb5c342ac92a5be795a044835
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09006444B2

Reaction notes

Loading…