Dimethylformamide → (5S)-5-({[4-[(2-Cyclopropylpyrimidin-5-yl)ethynyl]-3,6-dihydropyridin-1(2H)-yl]sulfonyl}methyl)-5-methylimidazolidine-2,4-dione

HRID 1669652Notes

Reaction equation

HRID 1669652 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([CH:8]2[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[C:11]([C:13]1[CH2:14][CH2:15][N:16]([S:19]([CH2:22]N2C(C)C(=O)NC2=O)(=[O:21])=[O:20])[CH2:17][CH:18]=1)#[CH:12].[CH3:31][CH2:32][N:33](CC)CC.C[N:39]([CH:41]=[O:42])[CH3:40].C1C[O:46]CC1>[Cu]I.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>[CH:8]1([C:5]2[N:4]=[CH:3][C:2]([C:12]#[C:11][C:13]3[CH2:14][CH2:15][N:16]([S:19]([CH2:22][C@@:32]4([CH3:31])[NH:33][C:40](=[O:46])[NH:39][C:41]4=[O:42])(=[O:20])=[O:21])[CH2:17][CH:18]=3)=[CH:7][N:6]=2)[CH2:10][CH2:9]1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 204444135-Bromo-2-cyclopropylpyrimidineHCID 86642353{[(4-ethynyl-3,6-dihydropyridin-1(2H)-yl)sulfonyl]methyl}-5-methylimidazolidine-2,4-dione

Product 1

HCID 11553444(5S)-5-({[4-[(2-Cyclopropylpyrimidin-5-yl)ethynyl]-3,6-dihydropyridin-1(2H)-yl]sulfonyl}methyl)-5-methylimidazolidine-2,4-dione

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
72 °C

Procedure

The title compound was prepared following the general method of Yamanaka et al, Synth. Commun., 1983, 312-314. To 5-bromo-2-cyclopropylpyrimidine (110 mg, 0.55 mmol) and (5S)-5-({[(4-ethynyl-3,6-dihydropyridin-1(2H) -yl)sulfonyl]methyl}-5-methylimidazolidine-2,4-dione (180 mg, 0.61 mmol) in THF (3 mL) was added Et3N (1 mL) and DMF (1 mL) at 35° C. After a solution was formed, CuI (4 mol %) and PdCl2(PPh3)2 (2 mol %) were added and the mixture was heated at 72° C. for 6 hours. The mixture was partitioned between EtOAc (15 mL) and water (10 mL), and the aqueous layer was extracted three times with EtOAc. The combined organic layers were dried and concentrated to give the crude product as a yellow oil. The title compound (65 mg) was obtained by purification using preparative HPLC.

Workup

  1. customAfter a solution was formed
  2. customThe mixture was partitioned between EtOAc (15 mL) and water (10 mL)
  3. extractionthe aqueous layer was extracted three times with EtOAc
  4. customThe combined organic layers were dried
  5. concentrationconcentrated
  6. customto give the crude product as a yellow oil

Sources & evidence

ORD record
ord-0272ddaf30ba43408e948cdbc1af6007
Source dataset
uspto-grants-2011_08
Patent number
US07989620B2

Reaction notes

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