Cesium carbonate → HCID 58456133, compound

HRID 410419Notes

Reaction equation

HRID 410419 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([Cl: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+]>[Cl-].[Na+].O.O>[Cl: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

7

Reactant 4

HCID 10796Cesium carbonateHCID 5906412,5-DichloropyrimidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58456365HCID 58456365, compound

Product 1

HCID 58456133HCID 58456133, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
110 °C

Procedure

A flask containing 2,5-dichloropyrimidine (2 g, 13.42 mmol), 3-methyl-5-(1,3-thiazol-5-yl)aniline (2.55 g, 13.42 mmol), PdOAc2 (0.603 g, 2.68 mmol), Xantphos (2.330 g, 4.03 mmol), and cesium carbonate (8.75 g, 26.8 mmol) was degassed for 5 min. Dioxane (89 ml) was added and argon was bubbled through the mixture for 15 min. The temperature was increased to 110° C. and the reaction was stirred 14 h at that temperature. The cooled reaction was diluted with brine and water and extracted three times with CH2Cl2. The organic layer was concentrated under reduced pressure and purified by flash chromatography (0-70% EtOAc:Hexanes) to give 5-chloro-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine (2.95 g, 73%) as a white solid. MS ESI: [M+H]+ m/z 303. 1H NMR (500 MHz, CDCl3) δ 8.75 (s, 1H), 8.37 (s, 2H), 8.08 (s, 1H), 7.71 (s, 1H), 7.33 (s, 1H), 7.09 (s, 1H), 2.40 (s, 3H). rhSYK activity=++.

Workup

  1. customwas degassed for 5 min
  2. additionDioxane (89 ml) was added
  3. customargon was bubbled through the mixture for 15 min
  4. customThe cooled reaction
  5. extractionextracted three times with CH2Cl2
  6. concentrationThe organic layer was concentrated under reduced pressure
  7. custompurified by flash chromatography (0-70% EtOAc:Hexanes)

Sources & evidence

ORD record
ord-cf4edad9232a43e38c98bdd15b1977a3
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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