Triethylamine → Tert-butyl 4-((4-amino-6-chloropyrimidin-5-yl)ethynyl)piperidine-1-carboxylate

HRID 527987Notes

Reaction equation

HRID 527987 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH2:8])[C:3]=1I.C(N(CC)CC)C.[C:17]([CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)#[CH:18]>CN(C)C=O.O.[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[NH2:8][C:4]1[C:3]([C:18]#[C:17][CH:19]2[CH2:20][CH2:21][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:23][CH2:24]2)=[C:2]([Cl:1])[N:7]=[CH:6][N:5]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 15550481tert-Butyl 4-ethynylpiperidine-1-carboxylateHCID 468558336-Chloro-5-iodopyrimidin-4-amine

Product 1

HCID 90418839Tert-butyl 4-((4-amino-6-chloropyrimidin-5-yl)ethynyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a degassed solution of Example 1A (400 mg, 1.6 mmol) in N,N-dimethylformamide (6 mL) was added copper (I) iodide (120 mg, 0.63 mmol) and triethylamine (2 mL, 14.33 mmol). The mixture was degassed for 5 minutes and tert-butyl 4-ethynylpiperidine-1-carboxylate (1.67 g, 7.98 mmol) and bis(triphenylphosphine) palladium(II)chloride (220 mg, 0.31 mmol) were added. The mixture was stirred at room temperature for 3 hours and diluted with water and extracted with ethyl acetate. The ethyl acetate layers were washed with water and brine, dried over sodium sulfate, filtered, and concentrated. Purification by column chromatography (silica gel, 30% ethyl acetate in hexane) afforded the title compound. LCMS: 337.1 (M+1)+.

Workup

  1. customThe mixture was degassed for 5 minutes
  2. extractionextracted with ethyl acetate
  3. washThe ethyl acetate layers were washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by column chromatography (silica gel, 30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-9649bca08b374e04b8d3fdf4f2fb6e53
Source dataset
uspto-grants-2016_05
Patent number
US09346813B2

Reaction notes

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