Cesium carbonate → N'-(5-chloro-1,3-benzodioxol-4-yl)-N-[2-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]pyrimidine-2,4-diamine

HRID 2237414

Reaction equation

HRID 2237414 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[C:4]([N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)[N:3]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:65]1[N:70]=[C:69]([NH:71][C:72]2[C:80]3[O:79][CH2:78][O:77][C:76]=3[CH:75]=[CH:74][C:73]=2[Cl:81])[CH:68]=[CH:67][N:66]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:81][C:73]1[CH:74]=[CH:75][C:76]2[O:77][CH2:78][O:79][C:80]=2[C:72]=1[NH:71][C:69]1[CH:68]=[CH:67][N:66]=[C:65]([NH:8][C:6]2[CH:5]=[C:4]([N:9]3[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]3)[N:3]=[C:2]([CH3:1])[N:7]=2)[N:70]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 426316842-chloro-N-(5-chloro-1,3-benzodioxol-4-yl)pyrimidin-4-amineHCID 570042202-Methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-amine

Product 1

HCID 42645269N'-(5-chloro-1,3-benzodioxol-4-yl)-N-[2-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]pyrimidine-2,4-diamineYield 16%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

2-Methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-amine (71 mg), palladium acetate (1 mg), Xantphos (24 mg), caesium carbonate (166 mg) and 2-chloro-N-(5-chloro-1,3-benzodioxol-4-yl)pyrimidin-4-amine (117 mg) were dissolved in dioxane (4 ml) under nitrogen and heated in a microwave reactor at 150° C. for 60 minutes. The reaction was cooled and partitioned between ethyl acetate and water. The organic layer was dried and concentrated to give a brown solid that was purified by reverse phase chromatography to give N′-(5-chloro-1,3-benzodioxol-4-yl)-N-[2-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]pyrimidine-2,4-diamine as a yellow solid (25 mg, 13%); NMR Spectrum (300 MHz, CDCl3) 2.30 (s, 3H), 2.37 (s, 3H), 2.55 (br s, 4H), 3.64 (br s, 4H), 5.90 (s, 2H), 5.95 (d, 1H), 6.58-6.68 (m, 1H), 6.78-6.95 (m, 1H), 7.40 (s, 1H), 8.09 (d, 1H); Mass Spectrum M+ 455.

Workup

  1. temperatureThe reaction was cooled
  2. custompartitioned between ethyl acetate and water
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. customto give a brown solid that
  6. customwas purified by reverse phase chromatography

Sources & evidence

ORD record
ord-46f0e1c01e0e409b996fcb7cb1d86f94
Source dataset
uspto-grants-2010_05
Patent number
US07718653B2

Linked notes

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