Cesium carbonate → 2-(2-Methoxy-ethylamino)-5-(pyrimidin-5-ylamino)-pyrimidine-4-carboxylic acid ethyl ester

HRID 467739Notes

Reaction equation

HRID 467739 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:11](Br)=[CH:10][N:9]=[C:8]([NH:13][CH2:14][CH2:15][O:16][CH3:17])[N:7]=1)=[O:5])[CH3:2].[NH2:18][C:19]1[CH:20]=[N:21][CH:22]=[N:23][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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>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]>[CH2:1]([O:3][C:4]([C:6]1[C:11]([NH:18][C:19]2[CH:20]=[N:21][CH:22]=[N:23][CH:24]=2)=[CH:10][N:9]=[C:8]([NH:13][CH2:14][CH2:15][O:16][CH3:17])[N:7]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 344373Pyrimidin-5-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58368043Ethyl 5-bromo-2-((2-methoxyethyl)amino)pyrimidine-4-carboxylate

Product 1

HCID 700975102-(2-Methoxy-ethylamino)-5-(pyrimidin-5-ylamino)-pyrimidine-4-carboxylic acid ethyl ester

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
130 °C

Procedure

A microwave reaction tube was charged with a suspension of 5-bromo-2-(2-methoxy-ethylamino)-pyrimidine-4-carboxylic acid ethyl ester (30 mg, 0.1 mmol), 5-aminopyrimidine (14 mg, 0.15 mmol) and cesium carbonate (45 mg, 0.14 mmol) in dioxane (0.6 ml) and flushed with argon. 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos; 19 mg, 32 μmol) and tris(dibenzylideneacetone)-dipalladium(0) chloroform adduct (10 mg, 10 μmol) were consecutively added and the reaction tube was sealed and stirred overnight at 130° C. After cooling-down to ambient temperature, the reaction mixture was filtrated. The filtrate was concentrated in vacuo and the product was obtained after purification by preparative HPLC using an acetonitrile/water gradient as yellow solid (11 mg, 35%).

Workup

  1. customA microwave reaction tube
  2. customflushed with argon
  3. customthe reaction tube was sealed
  4. filtrationAfter cooling-down to ambient temperature, the reaction mixture was filtrated
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe product was obtained
  7. customafter purification by preparative HPLC

Sources & evidence

ORD record
ord-feb0c6db266049e3946c75d395e35412
Source dataset
uspto-grants-2014_01
Patent number
US08623866B2

Reaction notes

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