2-Aminothiazole → 2-chloro-6-methyl-N-(1,3-thiazol-2-yl)pyrimidin-4-amine

HRID 383801Notes

Reaction equation

HRID 383801 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([CH3:9])[N:3]=1.[S:10]1[CH:14]=[CH:13][N:12]=[C:11]1[NH2:15].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd]>[Cl:1][C:2]1[N:7]=[C:6]([NH:15][C:11]2[S:10][CH:14]=[CH:13][N:12]=2)[CH:5]=[C:4]([CH3:9])[N:3]=1

Participants

7

Reactant 4

HCID 21552-AminothiazoleHCID 62657Potassium Phosphate, TribasicHCID 794712,4-Dichloro-6-methylpyrimidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)

Product 1

HCID 574407632-chloro-6-methyl-N-(1,3-thiazol-2-yl)pyrimidin-4-amine

Reagents, catalysts & solvents 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To the mixture of 2,4-dichloro-6-methylpyrimidine (507.7 mg), 1,3-thiazol-2-amine (345.0 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (289.1 mg) and K3PO4 (936.3 mg) in dioxane (20 ml) was added Pd2(dba)3 CHCl3 (255.9 mg). And the suspension was stirred at 85° C. overnight. The mixture was cooled to room temperature. The insoluble material was filtered off and washed with EtOAc. The filtrate was poured into saturated aqueous solution of NaHCO3 and extracted with EtOAc. The extract was washed with brine, dried over Na2SO4 and concentrated. The residue was purified with silica gel column chromatography (eluent: CHCl3/MeOH=98/2˜90/10) to give 2-chloro-6-methyl-N-(1,3-thiazol-2-yl)pyrimidin-4-amine as an orange solid.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationThe insoluble material was filtered off
  3. washwashed with EtOAc
  4. additionThe filtrate was poured into saturated aqueous solution of NaHCO3
  5. extractionextracted with EtOAc
  6. washThe extract was washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified with silica gel column chromatography (eluent: CHCl3/MeOH=98/2˜90/10)

Sources & evidence

ORD record
ord-6f33fe44863944ffb1c8649ddccb4ffb
Source dataset
uspto-grants-2013_02
Patent number
US08367690B2

Reaction notes

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