Sodium Hydroxide → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-(5-pyrimidinyl)-1-benzofuran-2-carboxamide hydrochloride

HRID 1012784Notes

Reaction equation

HRID 1012784 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][CH:12]=[N:13][CH:14]=2)O1.[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[CH:38]=[CH:37][C:36](Br)=[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[CH:38]=[CH:37][C:36]([C:9]4[CH:14]=[N:13][CH:12]=[N:11][CH:10]=4)=[CH:35][C:33]=3[CH:34]=1)=[O:29])[CH2:20]2

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 4192667Pyrimidine-5-boronic acid, pinacol esterHCID 67314004N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-bromo-1-benzofuran-2-carboxamide hydrochloride

Product 1

HCID 67314109N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-(5-pyrimidinyl)-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
90 °C

Procedure

177 mg (0.86 mmol) of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine and 2.15 ml of 1N sodium hydroxide solution are added to a mixture of 250 mg (0.72 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-5-bromo-1-benzofuran-2-carboxamide (Example 3A) and 52 mg (0.07 mmol) of PdCl2(dppf) in 3 ml of DMF. The reaction mixture is heated at 90° 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 is dissolved in methanol, and an excess of 1N hydrochloric acid is added. The solvent is removed under reduced pressure. Recrystallization of the residue from isopropanol and drying under high vacuum results in 28 mg (10% of theory) of the title compound.

Workup

  1. customThe solvent is removed under reduced pressure
  2. filtrationfiltered through kieselguhr
  3. customPurification
  4. dissolutionThe product is dissolved in methanol
  5. additionan excess of 1N hydrochloric acid is added
  6. customThe solvent is removed under reduced pressure
  7. customRecrystallization of the residue from isopropanol
  8. customdrying under high vacuum

Sources & evidence

ORD record
ord-6383b081c32d4208919e78790e327184
Source dataset
uspto-grants-2011_07
Patent number
US07977485B2

Reaction notes

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