Dichloromethane → 1-(benzo[d][1,3]dioxol-5-yl)-N-(6-(2-methoxybenzyl)pyridin-3-yl)cyclopropanecarboxamide

HRID 2069350Notes

Reaction equation

HRID 2069350 reaction equation
[Cl-].[CH3:2][O:3][C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH2:6][Zn+].C(Cl)Cl.[O:15]1[C:19]2[CH:20]=[CH:21][C:22]([C:24]3([C:27]([NH:29][C:30]4[CH:31]=[N:32][C:33](Br)=[CH:34][CH:35]=4)=[O:28])[CH2:26][CH2:25]3)=[CH:23][C:18]=2[O:17][CH2:16]1.C(N(CC([O-])=O)CC(O)=O)CN(CC([O-])=O)CC(O)=O.[Na+].[Na+].[NH4+].[Cl-]>C1COCC1>[O:15]1[C:19]2[CH:20]=[CH:21][C:22]([C:24]3([C:27]([NH:29][C:30]4[CH:31]=[N:32][C:33]([CH2:6][C:5]5[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=5[O:3][CH3:2])=[CH:34][CH:35]=4)=[O:28])[CH2:26][CH2:25]3)=[CH:23][C:18]=2[O:17][CH2:16]1

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 8759EDTA disodium saltHCID 25517Ammonium ChlorideHCID 578561131-(benzo[d][1,3]dioxol-5-yl)-N-(6-bromopyridin-3-yl)cyclopropanecarboxamideHCID 178489474HCID 178489474, compound

Product 1

HCID 442063271-(benzo[d][1,3]dioxol-5-yl)-N-(6-(2-methoxybenzyl)pyridin-3-yl)cyclopropanecarboxamideYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
150 °C

Procedure

A solution of (2-methoxybenzyl)zinc(II) chloride (4.44 mL, 0.5 M, 2.20 mmol) in THF and (DPPF)2PdCl2.CH2Cl2 (45 mg, 0.056 mmol) was stirred at room temperature for 20 minutes. To this, a slurry of 1-(benzo[d][1,3]dioxol-5-yl)-N-(6-bromopyridin-3-yl)cyclopropanecarboxamide (200 mg, 0.56 mmol) in THF (4 mL) was added and the reaction mixture was heated to 150° C. in a microwave reactor for 10 minutes. The resulting material was cooled to room temperature. Na2EDTA and saturated aqueous NH4Cl were added to the reaction and the mixture was stirred at room temperature for 30 minutes. The product was extracted using dichloromethane. The organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel to yield 1-(benzo[d][1,3]dioxol-5-yl)-N-(6-(2-methoxybenzyl)pyridin-3-yl)cyclopropanecarboxamide (152 mg, 68%).

Workup

  1. temperatureThe resulting material was cooled to room temperature
  2. extractionThe product was extracted
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. customevaporated under reduced pressure
  5. customThe crude product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-e1cd911f609046eaa76d889af13d1490
Source dataset
uspto-grants-2012_10
Patent number
US08299099B2

Reaction notes

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