Cesium carbonate → (R)-4-(1-(2-bromo-4-chlorophenyl)-2,2,2-trifluoroethoxy)-6-chloropyrimidin-2-amine

HRID 1499190Notes

Reaction equation

HRID 1499190 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]([OH:14])[C:10]([F:13])([F:12])[F:11].[Cl:15][C:16]1[CH:21]=[C:20](Cl)[N:19]=[C:18]([NH2:23])[N:17]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1>[Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]([O:14][C:20]1[CH:21]=[C:16]([Cl:15])[N:17]=[C:18]([NH2:23])[N:19]=1)[C:10]([F:11])([F:12])[F:13]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 655222-Amino-4,6-dichloropyrimidineHCID 66742830(R)-1-(2-bromo-4-chlorophenyl)-2,2,2-trifluoroethanol2×

Product 1

HCID 117942233(R)-4-(1-(2-bromo-4-chlorophenyl)-2,2,2-trifluoroethoxy)-6-chloropyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (R)-1-(2-bromo-4-chlorophenyl)-2,2,2-trifluoroethanol (Intermediate 43) (400 mg, 1.4 mmol) in dioxane (25 mL) was added 4,6-dichloropyrimidin-2-amine (1.1 g, 7 mmol) and Cs2CO3 (1.3 g, 4 mmol). The mixture was heated for 24 h at 80° C. The reaction was then cooled to RT and filtered. The solvent was removed in vacuo, then CH2Cl2 and heptane was added. The solvent volume was reduced until a solid precipitated out. The solid was filtered and the procedure repeated several times to provide (R)-4-(1-(2-bromo-4-chlorophenyl)-2,2,2-trifluoroethoxy)-6-chloropyrimidin-2-amine as a white solid.

Workup

  1. temperatureThe reaction was then cooled to RT
  2. filtrationfiltered
  3. customThe solvent was removed in vacuo
  4. additionCH2Cl2 and heptane was added
  5. customprecipitated out
  6. filtrationThe solid was filtered

Sources & evidence

ORD record
ord-0fa8eb0d6cee4610bbc788972df3ba1d
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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