Sodium Hydroxide → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-[4-(4-morpholinyl)phenyl]-1-benzofuran-2-carboxamide hydrochloride

HRID 1012776

반응식

HRID 1012776 반응식
[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[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: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:35][C:33]=3[CH:34]=1)=[O:29])[CH2:20]2

참가 물질

6

반응물 3

HCID 14798Sodium HydroxideHCID 2795359(4-(Morpholin-4-yl)phenyl)boronic acidHCID 67314004N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-bromo-1-benzofuran-2-carboxamide hydrochloride

생성물 1

HCID 67314243N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-[4-(4-morpholinyl)phenyl]-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 4-(4-morpholinyl)phenylboronic acid 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 fractions are concentrated and dissolved in acetonitrile/water, and an excess of 1N hydrochloric acid is added. The solvent is removed under reduced pressure. Drying under high vacuum results in 23 mg (7% of theory) of the title compound.

후처리

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

출처 및 근거

ORD 기록
ord-93e578b9042d446aa202c84265289534
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07977485B2

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