Tetrahydrofuran → 1-(Benzo[d][1,3]dioxol-5-yl)-N-(2-benzylpyridin-4-yl)cyclopropane-carboxamide

HRID 2069360Notes

Reaction equation

HRID 2069360 reaction equation
[Br-].[CH2:2]([Zn+])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C1COCC1.[O:15]1[C:19]2[CH:20]=[CH:21][C:22]([C:24]3([C:27]([NH:29][C:30]4[CH:35]=[CH:34][N:33]=[C:32](Cl)[CH:31]=4)=[O:28])[CH2:26][CH2:25]3)=[CH:23][C:18]=2[O:17][CH2:16]1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:15]1[C:19]2[CH:20]=[CH:21][C:22]([C:24]3([C:27]([NH:29][C:30]4[CH:35]=[CH:34][N:33]=[C:32]([CH2:2][C:3]5[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=5)[CH:31]=4)=[O:28])[CH2:26][CH2:25]3)=[CH:23][C:18]=2[O:17][CH2:16]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 578561911-(Benzo[d][1,3]dioxol-5-yl)-N-(2-chloropyridin-4-yl)cyclopropanecarboxamideHCID 178419772HCID 178419772, compound

Product 1

HCID 578561261-(Benzo[d][1,3]dioxol-5-yl)-N-(2-benzylpyridin-4-yl)cyclopropane-carboxamideYield 48%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Procedure

To a 0.5 M solution of benzylzinc(II) bromide in THF (0.8 mL, 0.4 mmol) was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (8 mg, 0.01 mmol) and the reaction was stirred under nitrogen for 20 minutes. 1-(Benzo[d][1,3]dioxol-5-yl)-N-(2-chloropyridin-4-yl)cyclopropanecarboxamide (32 mg, 0.10 mmol) was added and the reaction was irradiated in the microwave for 10 minutes at 150° C. The reaction was quenched with a saturated ammonium chloride solution (2 mL) and a saturated ethylenediamine tetraacetic acid disodium salt solution (2 mL). The mixture was stirred for 30 minutes before it was extracted with dichloromethane (3×4 mL). The organics were dried over Na2SO4 and evaporated. The crude product was dissolved in DMSO (1 mL) and purified by reverse-phase preparative liquid chromatography utilizing a gradient of 0-99% acetonitrile in water containing 0.05% trifluoracetic acid to yield the pure product (18 mg, 0.048 mmol, 48%). ESI-MS m/z calc. 372.1, found 373.3 (M+1)+; retention time 2.44 minutes.

Workup

  1. customthe reaction was irradiated in the microwave for 10 minutes at 150° C
  2. customThe reaction was quenched with a saturated ammonium chloride solution (2 mL)
  3. stirringThe mixture was stirred for 30 minutes before it
  4. extractionwas extracted with dichloromethane (3×4 mL)
  5. dry with materialThe organics were dried over Na2SO4
  6. customevaporated
  7. dissolutionThe crude product was dissolved in DMSO (1 mL)
  8. custompurified by reverse-phase preparative liquid chromatography

Sources & evidence

ORD record
ord-a27eaae8edad435da70e655d0f25182f
Source dataset
uspto-grants-2012_10
Patent number
US08299099B2

Reaction notes

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