Tetrahydrofuran → 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-(2-chlorobenzyl)pyrazin-2-yl)cyclopropanecarboxamide

HRID 2069357Notes

Reaction equation

HRID 2069357 reaction equation
[Cl-].[Cl:2][C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH2:5][Zn+].C1COCC1.[O:16]1[C:20]2[CH:21]=[CH:22][C:23]([C:25]3([C:28]([NH:30][C:31]4[CH:36]=[N:35][C:34](Br)=[CH:33][N:32]=4)=[O:29])[CH2:27][CH2:26]3)=[CH:24][C:19]=2[O:18][CH2:17]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:16]1[C:20]2[CH:21]=[CH:22][C:23]([C:25]3([C:28]([NH:30][C:31]4[CH:36]=[N:35][C:34]([CH2:5][C:4]5[CH:7]=[CH:8][CH:9]=[CH:10][C:3]=5[Cl:2])=[CH:33][N:32]=4)=[O:29])[CH2:27][CH2:26]3)=[CH:24][C:19]=2[O:18][CH2:17]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 578561451-(Benzo[d][1,3]dioxol-5-yl)-N-(5-bromopyrazin-2-yl)cyclopropanecarboxamideHCID 178478034HCID 178478034, compound

Product 1

HCID 578561421-(benzo[d][1,3]dioxol-5-yl)-N-(5-(2-chlorobenzyl)pyrazin-2-yl)cyclopropanecarboxamideYield 39%

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 (2-chlorobenzyl)zinc(II) chloride 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-(5-bromopyrazin-2-yl)cyclopropanecarboxamide (36 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 (16 mg, 0.039 mmol, 39%). ESI-MS m/z calc. 407.1, found 408.2 (M+1)+; retention time 3.82 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-51a02a293ccb41b2969ebb0c850d7edf
Source dataset
uspto-grants-2012_10
Patent number
US08299099B2

Reaction notes

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