1,4-Dioxane → HCID 58095248, compound

HRID 2282141Notes

Reaction equation

HRID 2282141 reaction equation
[CH2:1]([N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[C:9]1[S:13][C:12](Br)=[C:11]([C:15]#[N:16])[C:10]=1[C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=1[Cl:24])[CH:2]=[CH2:3].[CH3:25][O:26][C:27]1[CH:47]=[CH:46][C:30]([CH2:31][N:32]([C:36]2[CH:41]=[C:40]([Sn](C)(C)C)[CH:39]=[CH:38][N:37]=2)[C:33](=[O:35])[CH3:34])=[CH:29][CH:28]=1.O1CCOCC1>CCOC(C)=O.C(Cl)Cl.[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>[CH2:1]([N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[C:9]1[S:13][C:12]([C:40]2[CH:39]=[CH:38][N:37]=[C:36]([N:32]([CH2:31][C:30]3[CH:29]=[CH:28][C:27]([O:26][CH3:25])=[CH:47][CH:46]=3)[C:33](=[O:35])[CH3:34])[CH:41]=2)=[C:11]([C:15]#[N:16])[C:10]=1[C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=1[Cl:24])[CH:2]=[CH2:3]

Participants

7

Reactant 3

HCID 312751,4-DioxaneHCID 58094972HCID 58094972, compoundHCID 58095016HCID 58095016, compound

Product 1

HCID 58095248HCID 58095248, compoundYield 84.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 21226138Dichloromethane ethylacetateSolvent

Procedure

The mixture of 5-(1-allyl-1H-imidazol-2-yl)-2-bromo-4-(2,4-dichlorophenyl)thiophene-3-carbonitrile (0.840 g, 1.91 mmol), N-(4-methoxybenzyl)-N-[4-(trimethylstannyl)pyridin-2-yl]acetamide (0.992 g, 2.37 mmol) Lithium chloride (0.232 g, 5.46 mmol), Copper(I) iodide (0.104 g, 0.546 mmol) and Tetrakis(triphenylphosphine)palladium(0) (0.210 g, 0.182 mmol) in dry 1,4-Dioxane (50 mL, 600 mmol) was heated under N2 to reflux for 1 hour. The mixture was cooled to r.t., evaporated in rotavapor. The residue was quenched with aqueous saturated NaHCO3, extracted with DCM (2×150 mL), washed with water, brine, dried over Na2SO4, filtered, evaporated in rotavapor to give a brown solid. The solid was heated in EtOAc/DCM (50 mL/15 mL) to reflux for 15 min, cooled to r.t., filtered and washed with small amount of EtOAc. The filtrate was purified on a silica column using hexane as solvent A and hexane:concentrated aqueous NH4OH:MeOH:DCM (67%:0.5%:10.5%:22%) as solvent B (A/B from 100/0 to 0/100 in 5 min then 100% B for 10 min) to give a solid product (1.32 g, 75% pure by LCMS, yield 84.2%). LCMS: (AA) ES+, 614, 616. The product was used for next step without further purification.

Workup

  1. temperaturewas heated under N2
  2. temperatureto reflux for 1 hour
  3. customevaporated in rotavapor
  4. customThe residue was quenched with aqueous saturated NaHCO3
  5. extractionextracted with DCM (2×150 mL)
  6. washwashed with water, brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated in rotavapor
  10. customto give a brown solid
  11. temperatureto reflux for 15 min
  12. temperaturecooled to r.t.
  13. filtrationfiltered
  14. washwashed with small amount of EtOAc
  15. customThe filtrate was purified on a silica column
  16. custom100% B for 10 min) to give a solid product (1.32 g, 75% pure by LCMS, yield 84.2%)
  17. customThe product was used for next step without further purification

Sources & evidence

ORD record
ord-6c67a735e8f34fb888b4136aca15d54f
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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