Cesium carbonate → 2-[4-(tert-Butyl-dimethyl-silanyloxymethyl)-6-chloro-pyridin-2-ylamino]-thiazole-5-carbonitrile

HRID 1814006Notes

Reaction equation

HRID 1814006 reaction equation
[C:1]([SiH2:5][O:6][C:7]([CH3:17])([CH3:16])[C:8]1[CH:13]=[C:12]([Cl:14])[N:11]=[C:10]([NH2:15])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].Cl[C:19]1[S:20][C:21]([C:24]#[N:25])=[CH:22][N:23]=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>O.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].O1CCOCC1>[C:1]([SiH2:5][O:6][C:7]([CH3:17])([CH3:16])[C:8]1[CH:13]=[C:12]([Cl:14])[N:11]=[C:10]([NH:15][C:19]2[S:20][C:21]([C:24]#[N:25])=[CH:22][N:23]=2)[CH:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 14852222-Chlorothiazole-5-carbonitrileHCID 1317248184-(2-Tert-butylsilyloxypropan-2-yl)-6-chloropyridin-2-amine

Product 1

HCID 1317248192-[4-(tert-Butyl-dimethyl-silanyloxymethyl)-6-chloro-pyridin-2-ylamino]-thiazole-5-carbonitrile

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

An oven dried flask under N2 was charged with 4-(tert-butyl-dimethyl-silanyloxymethyl)-6-chloro-pyridin-2-ylamine (11-5, 0.488 g, 1.79 mmol), 2-chloro-5-cyanothiazole (1-2, 0.310 g, 2.15 mmol), cesium carbonate (0.816 g, 2.50 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.033 g, 0.040 mmol) and Xantphos (0.062 g, 0.060 mmol). Anhydrous dioxane, 6 mL, was added and the reaction was heated to reflux. After 3 hours the reaction was cooled to room temperature and stirred overnight. The reaction was diluted with water and extracted 3× with DCM. The extracts were dried over Na2SO4, filtered and concentrated. The resulting solid was triturated with ether, and filtered to afford the product as a tan solid.

Workup

  1. customAn oven dried flask under N2
  2. temperaturethe reaction was heated to reflux
  3. extractionextracted 3× with DCM
  4. dry with materialThe extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting solid was triturated with ether
  8. filtrationfiltered

Sources & evidence

ORD record
ord-a3266913e02b4a78b83ae5f121981f20
Source dataset
uspto-grants-2005_04
Patent number
US06875767B2

Reaction notes

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