Ethyl Acetate → (S)-tert-butyl (1-((5-(2-chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate

HRID 2284822Notes

Reaction equation

HRID 2284822 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH3:11])[C:5](I)=[CH:4][N:3]=1.[CH3:13][N:14]([C@@H:22]([CH3:31])[C:23](=[O:30])[NH:24][CH2:25][CH2:26][CH2:27][C:28]#[CH:29])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18].[Cl-].[NH4+].C(OCC)(=O)C>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>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH3:11])[C:5]([C:29]#[C:28][CH2:27][CH2:26][CH2:25][NH:24][C:23](=[O:30])[C@@H:22]([N:14]([CH3:13])[C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:20])[CH3:19])[CH3:31])=[CH:4][N:3]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 900517702-chloro-5-iodo-N-propylpyrimidin-4-amineHCID 90052832(S)-tert-butyl methyl(1-oxo-1-(4-pentyn-1-ylamino)propan-2-yl)carbamate

Product 1

HCID 90052304(S)-tert-butyl (1-((5-(2-chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamateYield 84.6%

Reagents, catalysts & solvents 4

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

Procedure

To a solution of 2-chloro-5-iodo-N-propylpyrimidin-4-amine (F1, 2.00 g) and (S)-tert-butyl methyl(1-oxo-1-(4-pentyn-1-ylamino)propan-2-yl)carbamate (U4, 2.16 g) in N,N-dimethylformamide (40 mL), triethylamine (4.67 mL), bis(triphenylphosphine)palladium(II) dichloride (0.47 g) and copper(I) iodide (0.26 g) were added at room temperature, and the mixture was stirred at the same temperature for 1.5 hours, and then further stirred at 45° C. for 0.5 hour. The reaction mixture was cooled to room temperature, and then saturated aqueous ammonium chloride and ethyl acetate were added to the reaction mixture. The organic layer was separated, washed with 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, 80 to 30% hexane in ethyl acetate) to obtain (S)-tert-butyl (1-((5-(2-chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate (V1, 2.49 g) as pale yellow oil.

Workup

  1. stirringfurther stirred at 45° C. for 0.5 hour
  2. customThe organic layer was separated
  3. washwashed with 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, 80 to 30% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-868d0058ea704affa8fc67cd0b84c438
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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