Cesium carbonate → 5-fluoro-4-methyl-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine

HRID 1039910Notes

Reaction equation

HRID 1039910 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([F:9])=[CH:4][N:3]=1.[CH3:10][C:11]1[CH:12]=[C:13]([CH:15]=[C:16]([C:18]2[S:22][CH:21]=[N:20][CH:19]=2)[CH:17]=1)[NH2:14].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+]>>[F:9][C:5]1[C:6]([CH3:8])=[N:7][C:2]([NH:14][C:13]2[CH:15]=[C:16]([C:18]3[S:22][CH:21]=[N:20][CH:19]=3)[CH:17]=[C:11]([CH3:10])[CH:12]=2)=[N:3][CH:4]=1

Participants

5

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 207780732-Chloro-5-fluoro-4-methylpyrimidineHCID 58456365HCID 58456365, compound

Product 1

HCID 584562835-fluoro-4-methyl-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amineYield 57.4%

Conditions

Temperature
100 °C

Procedure

2-Chloro-5-fluoro-4-methylpyrimidine (500 mg, 3.41 mmol), 3-methyl-5-(1,3-thiazol-5-yl)aniline (649 mg, 3.41 mmol), PdOAc2 (77 mg, 0.341 mmol), Xantphos (296 mg, 0.512 mmol), and cesium carbonate (2223 mg, 6.82 mmol) were combined in a flask and degassed with Argon. Dioxane (12 mL) was added and the solution was degassed with Argon for 5 min. The mixture was heated to 100° C. for 2 h and then allowed to cool to room temperature. The mixture was diluted with Brine and EtOAc. The layers were separated and the aqueous portion was re-extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. Purification via silica gel flash chromatography (0-40% EtOAc:CH2Cl2) afforded 5-fluoro-4-methyl-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine (588 mg, 57%) as a beige solid. MS ESI: [M+H]+ m/z 301. 1H NMR (500 MHz, CDCl3) δ 8.75 (s, 1H), 8.33 (s, 2H), 8.09 (s, 1H), 7.74 (s, 1H), 7.33 (s, 1H), 7.08 (s, 1H), 2.40 (s, 3H). rhSYK activity=+++.

Workup

  1. customdegassed with Argon
  2. additionDioxane (12 mL) was added
  3. customthe solution was degassed with Argon for 5 min
  4. temperatureto cool to room temperature
  5. additionThe mixture was diluted with Brine and EtOAc
  6. customThe layers were separated
  7. extractionthe aqueous portion was re-extracted with EtOAc
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customPurification via silica gel flash chromatography (0-40% EtOAc:CH2Cl2)

Sources & evidence

ORD record
ord-f1344ac626924e61a172799c060a80d2
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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