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

HRID 1012784

반응식

HRID 1012784 반응식
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

참가 물질

6

반응물 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

생성물 1

HCID 67314109N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-(5-pyrimidinyl)-1-benzofuran-2-carboxamide hydrochloride

시약·촉매·용매 2

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

반응 조건

온도
90 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-6383b081c32d4208919e78790e327184
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07977485B2

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