2-Amino-4,6-dichloropyrimidine → 4-Chloro-6-(2-furanyl)-2-pyrimidinamine

HRID 254151Notes

Reaction equation

HRID 254151 reaction equation
C([Sn](CCCC)(CCCC)[C:6]1[O:7][CH:8]=[CH:9][CH:10]=1)CCC.[NH2:19][C:20]1[N:25]=[C:24](Cl)[CH:23]=[C:22]([Cl:27])[N:21]=1>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:19][C:20]1[N:21]=[C:22]([Cl:27])[CH:23]=[C:24]([C:6]2[O:7][CH:8]=[CH:9][CH:10]=2)[N:25]=1

Participants

5

Reactant 2

HCID 655222-Amino-4,6-dichloropyrimidineHCID 43936882-(Tributylstannyl)furan

Product 1

HCID 223243064-Chloro-6-(2-furanyl)-2-pyrimidinamineYield 57%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 2-(tributylstannyl)furan (35.7 g, 100 mmol) in DMF (100 mL) was treated with 2-amino-4,6-dichloropyrimidine (16.4 g, 100 mmol) and dichlorobis(triphenylphosphine)palladium (II) (3.51 g, 5.0 mmol). The suspension was stirred at 80° C. for 18 h, allowed to cool to room temperature and poured onto ice (400 g). The solid precipitate was filtered off, washed with water, dried in air, and the filtrate was extracted with EtOAc (300 mL), washed with water (100 mL), mixed with the solid precipitate and concentrated. The crude product was purified by chromatography [SiO2; EtOAc:toluene (0:1-1:9-2:3)] and the material with Rf 0.23 (isopropyl ether) was triturated with isohexane to give the title compound (11.1 g, 57%) as a yellow solid; mp. 133-140° C.; NMR δH (400 MHz, DMSO) 6.70 (1H, q, J 2.0 Hz), 6.95 (1H, s), 7.16 (2H, br s), 7.27 (1H, d, J 3.6 Hz) and 7.92 (1H, t, J 1.0 Hz).

Workup

  1. temperatureto cool to room temperature
  2. additionpoured onto ice (400 g)
  3. filtrationThe solid precipitate was filtered off
  4. washwashed with water
  5. customdried in air
  6. extractionthe filtrate was extracted with EtOAc (300 mL)
  7. washwashed with water (100 mL)
  8. additionmixed with the solid precipitate
  9. concentrationconcentrated
  10. customThe crude product was purified by chromatography [SiO2; EtOAc:toluene (0:1-1:9-2:3)]
  11. customthe material with Rf 0.23 (isopropyl ether) was triturated with isohexane

Sources & evidence

ORD record
ord-b47238b752264867847b322086626272
Source dataset
uspto-grants-2011_01
Patent number
US07875600B2

Reaction notes

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