Sodium Hydroxide → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[4-(4-morpholinyl)phenyl]-1-benzofuran-2-carboxamide hydrochloride

HRID 2179649Notes

Reaction equation

HRID 2179649 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10](B(O)O)=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[OH-].[Na+].[ClH:18].[N:19]12[CH2:26][CH2:25][CH:22]([CH2:23][CH2:24]1)[C@@H:21]([NH:27][C:28]([C:30]1[O:31][C:32]3[C:38](Br)=[CH:37][CH:36]=[CH:35][C:33]=3[CH:34]=1)=[O:29])[CH2:20]2>CN(C=O)C.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]>[ClH:18].[N:19]12[CH2:24][CH2:23][CH:22]([CH2:25][CH2:26]1)[C@@H:21]([NH:27][C:28]([C:30]1[O:31][C:32]3[C:38]([C:10]4[CH:11]=[CH:12][C:7]([N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)=[CH:8][CH:9]=4)=[CH:37][CH:36]=[CH:35][C:33]=3[CH:34]=1)=[O:29])[CH2:20]2

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 2795359(4-(Morpholin-4-yl)phenyl)boronic acidHCID 67313982N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzofuran-2-carboxamide hydrochloride

Product 1

HCID 67313152N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[4-(4-morpholinyl)phenyl]-1-benzofuran-2-carboxamide hydrochloride

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

444 mg (2.15 mmol) of 4-(4-morpholinyl)phenylboronic acid and 4.3 ml of 1N sodium hydroxide solution are added to a mixture of 0.500 mg (0.143 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzofuran-2-carboxamide hydrochloride (Example 30A) and 105 mg (0.14 mmol) of PdCl2(dppf) in 5 ml of DMF. The reaction mixture is heated at 100° C. overnight. The solvent is removed under reduced pressure, and the crude product is taken up in methanol and filtered through kieselguhr. Purification takes place by preparative HPLC. The product fractions are concentrated and dissolved in methanol, and an excess of 1N hydrochloric acid is added. The solvent is removed under reduced pressure. Drying under high vacuum results in 393 mg (59% of theory) of the title compound.

Workup

  1. customThe solvent is removed under reduced pressure
  2. filtrationfiltered through kieselguhr
  3. customPurification
  4. concentrationThe product fractions are concentrated
  5. dissolutiondissolved in methanol
  6. additionan excess of 1N hydrochloric acid is added
  7. customThe solvent is removed under reduced pressure
  8. customDrying under high vacuum

Sources & evidence

ORD record
ord-f8a94b8c877e4b5db15889ac257ec6e6
Source dataset
uspto-grants-2015_06
Patent number
US09067931B2

Reaction notes

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