Dimethylformamide → HCID 117861350, compound

HRID 2284820Notes

Reaction equation

HRID 2284820 reaction equation
I[C:2]1[C:3]([NH:17][CH3:18])=[N:4][C:5]([NH:8][C:9]2[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=2)[C:12]#[N:13])=[N:6][CH:7]=1.[C:19]([C@@H:21]1[CH2:26][CH2:25][CH2:24][C@H:23]([NH:27][C:28](=[O:40])[C@@H:29]([N:31]([CH3:39])[C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH3:30])[CH2:22]1)#[CH:20].CN(C)C=O.C(=O)([O-])O.[Na+]>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.C(OCC)(=O)C.C(N(CC)CC)C>[C:12]([C:11]1[CH:10]=[C:9]([NH:8][C:5]2[N:4]=[C:3]([NH:17][CH3:18])[C:2]([C:20]#[C:19][C@@H:21]3[CH2:26][CH2:25][CH2:24][C@H:23]([NH:27][C:28](=[O:40])[C@@H:29]([N:31]([CH3:39])[C:32](=[O:38])[O:33][C:34]([CH3:35])([CH3:37])[CH3:36])[CH3:30])[CH2:22]3)=[CH:7][N:6]=2)[CH:16]=[CH:15][CH:14]=1)#[N:13]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 90051817HCID 90051817, compoundHCID 90052291HCID 90052291, compound

Product 1

HCID 117861350HCID 117861350, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 3-((5-iodo-4-(methylamino)pyrimidin-2-yl)amino)benzonitrile (F219, 30 mg), tert-butyl ((S)-1-(((1S,3R)-3-ethynylcyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (U2, 39.5 mg), bis(triphenylphosphine)palladium(II) dichloride (5.96 mg) and copper(I) iodide (3.24 mg), N,N-dimethylformamide (1 mL) and triethylamine (59 μL) were added at room temperature, and the mixture was stirred at the same temperature for 4 hours. To the reaction mixture, saturated aqueous sodium hydrogencarbonate and ethyl acetate 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, 84 to 25% hexane in ethyl acetate) to obtain tert-butyl ((S)-1-(((1S,3R)-3-((2-((3-cyanophenyl)amino)-4-(methylamino)pyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (U3, 27.4 mg) as pale yellow solid.

Workup

  1. customThe organic layer was separated
  2. washwashed successively with saturated aqueous ammonium chloride, water and saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (eluent, 84 to 25% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-2ae8e240fa6947b793c2a3d0438909c2
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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