Water → HCID 117861302, compound

HRID 2284782Notes

Reaction equation

HRID 2284782 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[C:13]([NH:15][CH2:16][CH2:17][CH3:18])[C:12](I)=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.[C:20]([C@@H:22]1[CH2:27][CH2:26][CH2:25][C@H:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:23]1)#[CH:21].O.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>[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[C:13]([NH:15][CH2:16][CH2:17][CH3:18])[C:12]([C:21]#[C:20][C@@H:22]3[CH2:27][CH2:26][CH2:25][C@H:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34])[CH2:23]3)=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 90051756HCID 90051756, compoundHCID 90051794tert-butyl ((1S,3R)-3-ethynylcyclohexyl)carbamate

Product 1

HCID 117861302HCID 117861302, compoundYield 103.5%

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 N2-(3-fluorophenyl)-5-iodo-N4-propylpyrimidine-2,4-diamine (F2, 100 mg), bis(triphenylphosphine)palladium(II) dichloride (19 mg) and copper(I) iodide (10 mg) in N,N-dimethylformamide (2.7 mL), triethylamine (188 μL) and tert-butyl ((1S*,3R*)-3-ethynylcyclohexyl)carbamate (M3, 90 mg) were added at room temperature, and the mixture was stirred at the same temperature for 1 hour and 45 minutes. To the reaction mixture, water and ethyl acetate were added. The organic layer was separated, washed successively with saturated ammonium chloride and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 94 to 60% hexane in ethyl acetate) to obtain tert-butyl ((1S*,3R*)-3-((2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidin-5-yl)ethynyl)cyclohexyl)carbamate (M4, 130 mg) as yellow solid.

Workup

  1. customThe organic layer was separated
  2. washwashed successively with saturated ammonium chloride and saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (eluent, 94 to 60% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-2eaf16f5622e4b509b2fc9584c13e05e
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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