Triethylamine → HCID 66832503, compound

HRID 1914519Notes

Reaction equation

HRID 1914519 reaction equation
Cl[C:2]1[CH:7]=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[F:9][C:10]([F:21])([F:20])[C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH2:30]([N:32](CC)CC)C>C(COC)OC.O.[C-]#N.C([N+](CC)(CC)CC)C.C(Cl)Cl.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:9][C:10]([F:21])([F:20])[C:11]1[CH:16]=[CH:15][C:14]([C:6]2[N:5]=[CH:4][N:3]=[C:2]([C:30]#[N:32])[CH:7]=2)=[CH:13][CH:12]=1

Participants

10

Reactant 4

HCID 8471TriethylamineHCID 62657Potassium Phosphate, TribasicHCID 709434,6-DichloropyrimidineHCID 27343894-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 66832503HCID 66832503, compoundYield 50%

Reagents, catalysts & solvents 5

HCID 3014735Tetraethylammonium cyanideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

Nitrogen gas was bubbled through a suspension of 4,6-dichloropyrimidine (10.0 g, 67.1 mmol), 4-(trifluoromethyl)phenylboronic acid (12.7 g, 67.1 mmol) and K3PO4 (28.5 g, 134.2 mmol) in dimethoxyethane (280 mL) and H2O (70 mL) for 30 minutes. Tetrakis(triphenylphosphine)-palladium (3.99 g, 3.4 mmol) was added and the reaction mixture was heated to 90° C. for 24 hours. The reaction mixture was cooled to rt, H2O (200 mL) was added and the resulting mixture was extracted with EtOAc (2×100 mL). The organic layers were combined, washed with brine (2×50 mL), dried with Na2SO4, filtered and purified by flash column chromatography (100% CH2Cl2) to provide the desire product as an inseparable ˜3:1 mixture of the desired and bisarylated products (10.37 g, 60%). This mixture material was advanced without further purification. The mixture (1.4 g, 3.9 mmol (corrected for impurity) was taken up in acetonitrile (15 mL) and tetraethylammonium cyanide (1.2 g, 7.7 mmol) and triethylamine (0.78 g, 7.7 mmol) were added and the reaction mixture was heated to 80° C. for 1 hr. The reaction mixture was cooled to rt, taken up in CH2Cl2 (100 mL), washed with H2O (2×20 mL), dried with Na2SO4, filtered, concentrated and the resulting oil was purified by flash column chromatography (100% CH2Cl2) to provide the desired product (0.49 g, 50%). 1H NMR (500 MHz, CDCl3) δ 9.44 (d, J=1.4, 1H), 8.27 (d, J=8.1, 2H), 8.10 (d, J=1.4, 1H), 7.84 (d, J=10.2, 2H).

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. extractionthe resulting mixture was extracted with EtOAc (2×100 mL)
  3. washwashed with brine (2×50 mL)
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. custompurified by flash column chromatography (100% CH2Cl2)
  7. customto provide the desire product
  8. additionas an inseparable ˜3:1 mixture of the
  9. customThis mixture material was advanced without further purification
  10. temperaturethe reaction mixture was heated to 80° C. for 1 hr
  11. temperatureThe reaction mixture was cooled to rt
  12. washwashed with H2O (2×20 mL)
  13. dry with materialdried with Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customthe resulting oil was purified by flash column chromatography (100% CH2Cl2)

Sources & evidence

ORD record
ord-eb9811e280e6469eb8ca1b209ce4402b
Source dataset
uspto-grants-2013_12
Patent number
US08614201B2

Reaction notes

Loading…