2-(Di-tert-butylphosphino)biphenyl → 2-[4-(4-Mesylpiperazin-1-yl)anilino]-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine

HRID 1441304Notes

Reaction equation

HRID 1441304 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[N:12]([CH:13]([CH3:15])[CH3:14])[C:11]([CH3:16])=[N:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.Br[C:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:29][CH2:28][N:27]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:26][CH2:25]2)=[CH:20][CH:19]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>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.[Pd].[Pd].CO.C(Cl)Cl>[S:30]([N:27]1[CH2:28][CH2:29][N:24]([C:21]2[CH:20]=[CH:19][C:18]([NH:1][C:2]3[N:7]=[C:6]([C:8]4[N:12]([CH:13]([CH3:14])[CH3:15])[C:11]([CH3:16])=[N:10][CH:9]=4)[CH:5]=[CH:4][N:3]=3)=[CH:23][CH:22]=2)[CH2:25][CH2:26]1)([CH3:33])(=[O:31])=[O:32]

Participants

8

Reactant 4

HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 219193841-(4-Bromophenyl)-4-(methylsulfonyl)piperazineHCID 23676156Sodium t-butoxideHCID 25178483HCID 25178483, compound

Product 1

HCID 445785702-[4-(4-Mesylpiperazin-1-yl)anilino]-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
95 °C

Procedure

2-Amino-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine (Method 39 of WO 03/076436; 220 mg, 1 mmol), 1-bromo-4-(4-mesylpiperazinyl)benzene (WO 2001062742; 319 mg, 1 mmol), tris(dibenzylideneacetone)dipalladium(0) (23 mg, 2 mol %), 2-(di-tert-butylphosphino)biphenyl (6 mg, 2 mol %) and sodium tert-butoxide (135 mg, 1.4 mmol) in anhydrous 1,4-dioxane (10 ml) was evacuated and refilled with nitrogen (3 times). The reaction was heated under nitrogen at 95° C. overnight before evaporating under reduced pressure. The residue was triturated with EtOAc (20 ml), filtered and re-evaporated to give a gum. Chromatography on silica gel with MeOH:DCM (2:98 to 5:95) gave the title compound as a yellow solid. (70 mg 15%). NMR: 1.39 (d, 6H), 2.47 (s, 3H), 2.92 (s, 3H), 3.17 (m, 4H), 3.26 (m, 4H), 5.70 (septuplet, 1H), 6.92 (d, 2H), 6.94 (d, 1H), 7.39 (s, 1H), 7.48 (d, 2H), 8.32 (d, 1H), 9.18 (s, 1H); m/z 456.

Workup

  1. additionrefilled with nitrogen (3 times)
  2. custombefore evaporating under reduced pressure
  3. customThe residue was triturated with EtOAc (20 ml)
  4. filtrationfiltered
  5. customre-evaporated
  6. customto give a gum

Sources & evidence

ORD record
ord-9a51caf7f11a4df9a2eee20f2d7bf4b9
Source dataset
uspto-grants-2010_02
Patent number
US07655652B2

Reaction notes

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