Cesium carbonate → HCID 58456170, compound

HRID 410421Notes

Reaction equation

HRID 410421 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.[CH3:9][C:10]1[CH:11]=[C:12]([CH:14]=[C:15]([C:17]2[S:21][CH:20]=[N:19][CH:18]=2)[CH:16]=1)[NH2:13].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:8][C:5]1[CH:4]=[N:3][C:2]([NH:13][C:12]2[CH:14]=[C:15]([C:17]3[S:21][CH:20]=[N:19][CH:18]=3)[CH:16]=[C:10]([CH3:9])[CH:11]=2)=[N:7][CH:6]=1

Participants

5

Reactant 4

HCID 10796Cesium carbonateHCID 5834662-Chloro-5-fluoropyrimidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58456365HCID 58456365, compound

Product 1

HCID 58456170HCID 58456170, compoundYield 92.4%

Conditions

Temperature
100 °C

Procedure

2-Chloro-5-fluoropyrimidine (0.443 ml, 3.58 mmol), 3-methyl-5-(1,3-thiazol-5-yl)aniline (682 mg, 3.58 mmol), PdOAc2 (80 mg, 0.358 mmol), Xantphos (311 mg, 0.538 mmol), and cesium carbonate (2336 mg, 7.17 mmol) were combined in a flask and degassed with Argon. Dioxane (12 mL) was added and the mixture was degassed with Argon for 5 min. The mixture was then heated to 100° C. for 2 h. The reaction was cooled to room temperature, diluted with brine and EtOAc. The layers were separated and the aqueous portion re-extracted with EtOAc. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo. Purification via silica gel flash chromatography (0-40% EtOAc:CH2Cl2) afforded 5-fluoro-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine (947 mg, 92%) as a beige solid. MS ESI: [M+H]+ m/z 287. rhSYK activity=++.

Workup

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

Sources & evidence

ORD record
ord-2d010c68a2b6466f81bf021d919429de
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

Loading…