Trimethylsilylacetylene → N2-(2-Isopropoxy-4-methyl-5-trimethylsilanylethynyl-phenyl)-5-methyl-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine

HRID 388566Notes

Reaction equation

HRID 388566 reaction equation
Br[C:2]1[C:3]([CH3:33])=[CH:4][C:5]([O:29][CH:30]([CH3:32])[CH3:31])=[C:6]([NH:8][C:9]2[N:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[S:22]([CH:25]([CH3:27])[CH3:26])(=[O:24])=[O:23])[C:12]([CH3:28])=[CH:11][N:10]=2)[CH:7]=1.[C:34]([Si:36]([CH3:39])([CH3:38])[CH3:37])#[CH:35].C(N(CC)C(C)C)(C)C>O1CCOCC1.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.[Cu]I>[CH:30]([O:29][C:5]1[CH:4]=[C:3]([CH3:33])[C:2]([C:35]#[C:34][Si:36]([CH3:39])([CH3:38])[CH3:37])=[CH:7][C:6]=1[NH:8][C:9]1[N:14]=[C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[S:22]([CH:25]([CH3:27])[CH3:26])(=[O:24])=[O:23])[C:12]([CH3:28])=[CH:11][N:10]=1)([CH3:32])[CH3:31]

Participants

7

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 59764523N2-(5-Bromo-2-isopropoxy-4-methyl-phenyl)-5-methyl-N4-[2-(propane-2-sulfonyl)-phenyl]pyrimidine-2,4-diamine

Product 1

HCID 59764535N2-(2-Isopropoxy-4-methyl-5-trimethylsilanylethynyl-phenyl)-5-methyl-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
22 °C

Procedure

A mixture of N2-(5-Bromo-2-isopropoxy-4-methyl-phenyl)-5-methyl-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine (Example 5, Step 4, 110 mg, 0.21 mmol), ethynyl-trimethyl-silane (0.14 mL), N,N-diisopropyl ethylamine (0.10 mL), PdCl2(PhCN)2 (12 mg), tBu3PHBF4 (17 mg), and CuI (4 mg) in 1 mL 1,4-dioxane is stirred at 22° C. for 20 hrs followed by heating at 60° C. for an additional 2 hrs. The reaction mixture is filtered through a small Celite plug and concentrated. The residue is purified over a 4 g SiO2 column (ISCO) using a gradient of 0 to 20% ethyl acetate in hexanes as eluent, affording N2-(2-Isopropoxy-4-methyl-5-trimethylsilanylethynyl-phenyl)-5-methyl-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine as a yellow viscous oil.

Workup

  1. temperatureby heating at 60° C. for an additional 2 hrs
  2. filtrationThe reaction mixture is filtered through a small Celite plug
  3. concentrationconcentrated
  4. customThe residue is purified over a 4 g SiO2 column (ISCO)

Sources & evidence

ORD record
ord-b9b16b270e724c82ad47a66ad79d3d50
Source dataset
uspto-grants-2013_02
Patent number
US08377921B2

Reaction notes

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