Cesium carbonate → N-(5-Chloro-2-methoxypyridin-3-yl)-2-methylpyrimidin-4-amine

HRID 592909Notes

Reaction equation

HRID 592909 reaction equation
Br[C:2]1[C:3]([O:9][CH3:10])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:11][C:12]1[N:17]=[C:16]([NH2:18])[CH:15]=[CH:14][N:13]=1.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-])[O-].[Cs+].[Cs+]>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>[Cl:8][C:6]1[CH:7]=[C:2]([NH:18][C:16]2[CH:15]=[CH:14][N:13]=[C:12]([CH3:11])[N:17]=2)[C:3]([O:9][CH3:10])=[N:4][CH:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 2957632-Methylpyrimidin-4-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 135677513-Bromo-5-chloro-2-methoxypyridine

Product 1

HCID 86684411N-(5-Chloro-2-methoxypyridin-3-yl)-2-methylpyrimidin-4-amineYield 74%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (30 mL), 3-bromo-5-chloro-2-methoxypyridine (865 mg, 3.9 mmol), 2-methylpyrimidin-4-amine (327 mg, 3.0 mmol), Pd2(dba)3 (275 mg, 0.30 mmol), XantPhos (173.4 mg, 0.30 mmol), and cesium carbonate (1.96 g, 6.0 mmol). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 5 h. After this time the reaction was cooled to room temperature. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 5:1 ethyl acetate/petroleum ether to afford 222a (555 mg, 74%) as a white solid. MS-ESI: [M+H]+ 251.0

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureAfter this time the reaction was cooled to room temperature
  4. filtrationIt was then filtered
  5. customthe filtrate was evaporated in vacuo
  6. customThe residue was purified by silica-gel column chromatography
  7. washeluting with 5:1 ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-181fa90e6cb042909ccec644b9fb1135
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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