Tetrahydrofuran → 1-(Benzo[d][1,3]dioxol-5-yl)-N-(6-(cyclohexylmethyl)pyridin-2-yl)cyclopropanecarboxamide

HRID 39457Notes

Reaction equation

HRID 39457 reaction equation
[Br-].[CH:2]1([CH2:8][Zn+])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]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][CH:33]=[C:32](Br)[N: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][CH:33]=[C:32]([CH2:8][CH:2]5[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]5)[N: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 591658951-(Benzo[d][1,3]dioxol-6-yl)-N-(6-bromopyridin-2-yl)cyclopropanecarboxamideHCID 178419774HCID 178419774, compound

Product 1

HCID 578951241-(Benzo[d][1,3]dioxol-5-yl)-N-(6-(cyclohexylmethyl)pyridin-2-yl)cyclopropanecarboxamideYield 50%

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 (cyclohexylmethyl)zinc(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-(6-bromopyridin-2-yl)cyclopropanecarboxamide (36 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 (20 mg, 0.05 mmol, 50%). ESI-MS m/z calc. 378.19. found 379.1 (M+1)+; retention time 3.55 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-c9f09321b0224b418f0a24549a8c6cc8
Source dataset
uspto-grants-2013_09
Patent number
US08524910B2

Reaction notes

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