Ethyl Acetate → Diethyl 2-(4-(2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidin-5-yl)-2-methyl-3-butyn-2-yl)malonate

HRID 2284720Notes

Reaction equation

HRID 2284720 reaction equation
[CH3:1][C:2]([CH:6]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([C:4]#[CH:5])[CH3:3].[F:17][C:18]1[CH:19]=[C:20]([NH:24][C:25]2[N:30]=[C:29]([NH:31][CH2:32][CH2:33][CH3:34])[C:28](I)=[CH:27][N:26]=2)[CH:21]=[CH:22][CH:23]=1.C(OCC)(=O)C.[Cl-].[NH4+]>CN(C)C=O.C(N(CC)CC)C.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.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:17][C:18]1[CH:19]=[C:20]([NH:24][C:25]2[N:30]=[C:29]([NH:31][CH2:32][CH2:33][CH3:34])[C:28]([C:5]#[C:4][C:2]([CH:6]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:3])[CH3:1])=[CH:27][N:26]=2)[CH:21]=[CH:22][CH:23]=1

Participants

10

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 304028Diethyl (2-methylbut-3-yn-2-yl)propanedioateHCID 90051756HCID 90051756, compound

Product 1

HCID 90052124Diethyl 2-(4-(2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidin-5-yl)-2-methyl-3-butyn-2-yl)malonate

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of diethyl 2-(2-methyl-3-butyn-2-yl)malonate synthesized according to the method described in Chemistry A European Journal, 2005, 11, pp. 308-320 (3.3 g), N2-(3-fluorophenyl)-5-iodo-N4-propylpyrimidine-2,4-diamine (F2, 868 mg), bis(triphenylphosphine)palladium(II) dichloride (161 mg) and copper(I) iodide (88 mg) in N,N-dimethylformamide (15 mL), triethylamine (1.6 mL) was added at room temperature, and the mixture was stirred at the same temperature for 2 hours and 30 minutes. To the reaction mixture, tetrakis(triphenylphosphine)palladium(0) (132 mg) was added at room temperature, and the mixture was stirred at the same temperature for 1 hour and 40 minutes. To the reaction mixture, ethyl acetate and saturated aqueous ammonium chloride were added. The organic layer was separated, washed successively with saturated aqueous ammonium chloride, water and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 94 to 64% hexane in ethyl acetate) to obtain diethyl 2-(4-(2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidin-5-yl)-2-methyl-3-butyn-2-yl)malonate (F13, 803 mg) as yellow solid.

Workup

  1. stirringthe mixture was stirred at the same temperature for 1 hour and 40 minutes
  2. customThe organic layer was separated
  3. washwashed successively with saturated aqueous ammonium chloride, water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (eluent, 94 to 64% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-45eab6484675405c9473792c09e0cc15
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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