Triethylamine → Methyl 5-(N-{[6-amino-5-({3-[(3-methyl-2-furoyl)amino]phenyl}ethynyl)pyridin-3-yl]carbonyl}-S-methylsulfonimidoyl)pentanoate

HRID 1778137Notes

Reaction equation

HRID 1778137 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]=[S:11]([CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])([CH3:13])=[O:12])=[O:9])=[CH:4][C:3]=1I.[C:23]([C:25]1[CH:26]=[C:27]([NH:31][C:32]([C:34]2[O:35][CH:36]=[CH:37][C:38]=2[CH3:39])=[O:33])[CH:28]=[CH:29][CH:30]=1)#[CH:24].C(N(CC)CC)C>CN(C=O)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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]=[S:11]([CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])([CH3:13])=[O:12])=[O:9])=[CH:4][C:3]=1[C:24]#[C:23][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([NH:31][C:32]([C:34]2[O:35][CH:36]=[CH:37][C:38]=2[CH3:39])=[O:33])[CH:26]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 51337833N-(3-ethynylphenyl)-3-methylfuran-2-carboxamideHCID 118130089Methyl 5-{N-[(6-amino-5-iodopyridin-3-yl)carbonyl]-S-methylsulfonimidoyl}pentanoate

Product 1

HCID 118130044Methyl 5-(N-{[6-amino-5-({3-[(3-methyl-2-furoyl)amino]phenyl}ethynyl)pyridin-3-yl]carbonyl}-S-methylsulfonimidoyl)pentanoateYield 70%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

The solution of methyl 5-{N-[(6-amino-5-iodopyridin-3-yl)carbonyl]-S-methylsulfonimidoyl}pentanoate, (565 mg, 1.28 mmol) in anhydrous DMF (7 mL) was degassed with anhydrous nitrogen and then to the solution was added 3-methyl-furan-2-carboxylic acid (3-ethynyl-phenyl)-amide (376.5 mg, 1.3 eq), bis(triphenylphosphine)palladium(II) dichloride (90.3 mg, 0.1 eq), triphenyl phosphine (8.4 mg, 0.025 eq), triethylamine (0.75 mL, 4 eq) and lastly copper(I) iodide (50 mg, 0.2 eq) under anhydrous nitrogen atmosphere. The reaction mixture was stirred at RT for about 15 minutes and then partitioned between saturated aq NaHCO3 and EtOAc. The organic layer was washed one more time with saturated aq NaHCO3, then with aq NH4Cl (1×), brine (1×), and dried with anhydrous Na2SO4 overnight. The upper solution layer was decanted and concentrated. The oily residue was subject to gradient column chromatography. Concentration of the product eluting fractions gave the title compound as white foam (480 mg, 70%).

Workup

  1. custompartitioned between saturated aq NaHCO3 and EtOAc
  2. washThe organic layer was washed one more time with saturated aq NaHCO3
  3. dry with materialwith aq NH4Cl (1×), brine (1×), and dried with anhydrous Na2SO4 overnight
  4. customThe upper solution layer was decanted
  5. concentrationconcentrated
  6. washConcentration of the product eluting fractions

Sources & evidence

ORD record
ord-7bff272f2dc349b1926d48d9193e68b8
Source dataset
uspto-grants-2016_02
Patent number
US09266869B2

Reaction notes

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