Diethylamine → N-{4-[4-(diethylcarbamoyl-phenyl-methyl)-piperazin-1-yl]-3-trimethylsilanylethynyl-phenyl}-2-ethylbutyramide

HRID 1927633Notes

Reaction equation

HRID 1927633 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:28][C:29](=[O:35])[CH:30]([CH2:33][CH3:34])[CH2:31][CH3:32])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([CH:14]([C:21](=[O:27])[N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][CH2:9]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(NCC)C.[CH3:60][Si:61]([C:64]#[CH:65])([CH3:63])[CH3:62]>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:23]([N:22]([CH2:25][CH3:26])[C:21]([CH:14]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[N:11]1[CH2:12][CH2:13][N:8]([C:7]2[CH:6]=[CH:5][C:4]([NH:28][C:29](=[O:35])[CH:30]([CH2:33][CH3:34])[CH2:31][CH3:32])=[CH:3][C:2]=2[C:65]#[C:64][Si:61]([CH3:63])([CH3:62])[CH3:60])[CH2:9][CH2:10]1)=[O:27])[CH3:24]

Participants

8

Reactant 4

HCID 8021DiethylamineHCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 58870741HCID 58870741, compound

Product 1

HCID 69304338N-{4-[4-(diethylcarbamoyl-phenyl-methyl)-piperazin-1-yl]-3-trimethylsilanylethynyl-phenyl}-2-ethylbutyramideYield 16%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of N-{3-bromo-4-[4-(diethylcarbamoyl-phenyl-methyl)-piperazin-1-yl]-phenyl}-2-ethyl-butyramide (66 mg, 0.12 mmol) in DMF (1.5 mL) was added CuI (1.3 mg, 0.01 mmol), triphenylphosphine (73 mg, 0.28 mmol), diethylamine (220 μL, 2.1 mmol), trimethylsilylacetylene (22 μL, 0.15 mmol) and dichlorobis(triphenylphosphine)palladium (II) (5.0 mg, 0.01 mmol). This solution was heated in a focused microwave reactor at 120° C. for 5 min, after which the solution was concentrated and purified by reverse phase HPLC to provide N-{4-[4-(diethylcarbamoyl-phenyl-methyl)-piperazin-1-yl]-3-trimethylsilanylethynyl-phenyl}-2-ethylbutyramide (10.5 mg, 16%). This compound (18 mg, 0.03 mmol) was dissolved in MeOH and treated with K2CO3 (9.0 mg, 0.06 mmol). After 1 h, the solids were filtered off, the filtrate concentrated, and the product purified by reverse phase HPLC to afford the title compound (10 mg, 63%). MS: 489.4.

Workup

  1. concentrationafter which the solution was concentrated
  2. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-90e8387e826145388c6be5579ff5e721
Source dataset
uspto-grants-2012_05
Patent number
US08183239B2

Reaction notes

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