1,2-Dimethoxyethane → 2-Chloro-4-(2-chloro-pyridin-3-yl)-5-fluoro-pyrimidine

HRID 446302Notes

Reaction equation

HRID 446302 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[Cl:10][C:11]1[C:16](B(O)O)=[CH:15][CH:14]=[CH:13][N:12]=1.COCCOC.C([O-])(O)=O.[Na+]>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:16]2[C:11]([Cl:10])=[N:12][CH:13]=[CH:14][CH:15]=2)[C:5]([F:9])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 516892Sodium BicarbonateHCID 2762704(2-Chloropyridin-3-yl)boronic acid

Product 1

HCID 772302032-Chloro-4-(2-chloro-pyridin-3-yl)-5-fluoro-pyrimidine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To 2,4-dichloro-5-fluoropyrimidine (500 mg, 2.99 mmol), 2-chloropyridine-3-boronic acid (707 mg, 4.49 mmol), Pd(PPh3)4 (346 mg, 0.30 mmol) was added DME (9.0 mL) and 1 M NaHCO3 (3.0 mL). The mixture was heated overnight in a sealed tube at 80° C., cooled to RT, diluted with EtOAc, and washed with water and saturated Na2CO3. The organic layer was dried over Na2SO4, filtered, concentrated and purified by reverse-phase HPLC to provide 2-chloro-4-(2-chloro-pyridin-3-yl)-5-fluoro-pyrimidine. MS m/z=244, 246 [M]+ and [M+2]+. Calc'd for C9H4Cl2FN3: 244.06.

Workup

  1. temperaturecooled to RT
  2. washwashed with water and saturated Na2CO3
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-373728d4e35947deb6a1ee43491c8928
Source dataset
uspto-grants-2013_07
Patent number
US08476434B2

Reaction notes

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