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

HRID 2401941Notes

Reaction equation

HRID 2401941 reaction equation
[Cl-].[CH3:2][O:3][C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH2:6][Zn+].C1COCC1.[O:17]1[C:21]2[CH:22]=[CH:23][C:24]([C:26]3([C:29]([NH:31][C:32]4[N:33]=[N:34][C:35](Cl)=[CH:36][CH:37]=4)=[O:30])[CH2:28][CH2:27]3)=[CH:25][C:20]=2[O:19][CH2:18]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:17]1[C:21]2[CH:22]=[CH:23][C:24]([C:26]3([C:29]([NH:31][C:32]4[N:33]=[N:34][C:35]([CH2:6][C:5]5[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=5[O:3][CH3:2])=[CH:36][CH:37]=4)=[O:30])[CH2:28][CH2:27]3)=[CH:25][C:20]=2[O:19][CH2:18]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 578561941-(benzo[d][1,3]dioxol-5-yl)-N-(6-chloropyridazin-3-yl)cyclopropanecarboxamideHCID 178489474HCID 178489474, compound

Product 1

HCID 442065431-(benzo[d][1,3]dioxol-5-yl)-N-(6-(2-methoxybenzyl)pyridazin-3-yl)cyclopropanecarboxamideYield 52%

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-methoxybenzyl)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-(6-chloropyridazin-3-yl)cyclopropanecarboxamide (32 mg, 0.1 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 (21 mg, 0.052 mmol, 52%). ESI-MS m/z calc. 379.2, found 380.3 (M+1)+; retention time 3.54 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-89a6590d178446f9aa92e1447c6762aa
Source dataset
uspto-grants-2014_08
Patent number
US08796312B2

Reaction notes

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