1,4-Dioxane → HCID 66855533, compound

HRID 2282122Notes

Reaction equation

HRID 2282122 reaction equation
[C:1]([C:3]1[C:4]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=2[Cl:28])=[C:5]([C:9]2[N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][CH2:12][N:13]=2)[S:6][C:7]=1I)#[N:2].C[Sn](C)(C)[C:31]1[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38]([CH:40]2[CH2:42][CH2:41]2)=[O:39])[CH:32]=1.[Cl-].[Li+].O1CCOCC1>[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:3]1[C:4]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=2[Cl:28])=[C:5]([C:9]2[N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][CH2:12][N:13]=2)[S:6][C:7]=1[C:31]1[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38]([CH:40]2[CH2:41][CH2:42]2)=[O:39])[CH:32]=1)#[N:2]

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 433294Lithium ChlorideHCID 58094931HCID 58094931, compoundHCID 66854708HCID 66854708, compound

Product 1

HCID 66855533HCID 66855533, compoundYield 59.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

tert-butyl 2-[4-cyano-3-(2,4-dichlorophenyl)-5-iodo-2-thienyl]-4,5-dihydro-1H-imidazole-1-carboxylate (0.500 g, 0.912 mmol), N-[4-(trimethylstannyl)pyridin-2-yl]cyclopropanecarboxamide (0.445 g, 1.37 mmol), Lithium chloride (0.116 g, 2.74 mmol), Copper(I) iodide (0.0521 g, 0.274 mmol) and Tetrakis(triphenylphosphine)palladium(0) (0.105 g, 0.0912 mmol) were combined in a 100 mL round-bottom flask under an atmosphere of argon and 1,4-Dioxane (45.3 mL, 0.580 mol) was added. The solution was heated to reflux for 2 hours. The reaction was concentrated in vacuo and the residue was purified using ISCO chromatography on silica gel, elution 10 to 70% ethyl acetate in hexanes to afford the product (0.315 g, 59%). LCMS: (FA) ES+, 582, 584. 1H NMR (400 MHz, d1-chloroform) δ: 8.62-8.58 (m, 1H) 8.41-8.38 (m, 1H), 8.26 (s, 1H), 7.54-7.50 (m, 1H), 7.50-7.48 (m, 1H), 7.40-7.37 (m, 1H), 7.33-7.29 (m, 1H), 3.96-3.73 (m, 4H), 1.56-1.54 (m, 1H), 1.32 (s, 9H), 1.17-1.11 (m, 2H), 0.95-0.88 (m, 2H).

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 2 hours
  3. concentrationThe reaction was concentrated in vacuo
  4. customthe residue was purified
  5. washon silica gel, elution 10 to 70% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-b2179a940b214ce0ad30905f7730b789
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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