Sodium Carbonate → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-(3-methoxyphenyl)-1-benzothiophene-2-carboxamide hydrochloride

HRID 1012733노트

반응식

HRID 1012733 반응식
C(=O)([O-])[O-].[Na+].[Na+].[ClH:7].[N:8]12[CH2:15][CH2:14][CH:11]([CH2:12][CH2:13]1)[C@@H:10]([NH:16][C:17]([C:19]1[S:20][C:21]3[C:27](Br)=[CH:26][CH:25]=[CH:24][C:22]=3[CH:23]=1)=[O:18])[CH2:9]2.[CH3:29][O:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1>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:7].[N:8]12[CH2:15][CH2:14][CH:11]([CH2:12][CH2:13]1)[C@@H:10]([NH:16][C:17]([C:19]1[S:20][C:21]3[C:27]([C:35]4[CH:34]=[CH:33][CH:32]=[C:31]([O:30][CH3:29])[CH:36]=4)=[CH:26][CH:25]=[CH:24][C:22]=3[CH:23]=1)=[O:18])[CH2:9]2

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 2734370(3-Methoxyphenyl)boronic acidHCID 66904832N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

생성물 1

HCID 67313634N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-(3-methoxyphenyl)-1-benzothiophene-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
80 °C

실험 절차

0.16 ml of 2 M aqueous sodium carbonate solution and 4.2 mg (0.005 mmol) of PdCl2(dppf) are added to a mixture of 49 mg (0.10 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 8A) and 15.8 mg (0.10 mmol) of 3-methoxyphenylboronic acid in 1 ml of DMF. The reaction mixture is heated at 80° C. for 14 h, then filtered through kieselguhr and evaporated to dryness. Purification of the crude product by preparative HPLC, subsequent addition of 1N hydrochloric acid and drying under high vacuum result in 8.0 mg (18% of theory) of the title compound.

후처리

  1. filtrationfiltered through kieselguhr
  2. customevaporated to dryness
  3. customPurification of the crude product
  4. additionby preparative HPLC, subsequent addition of 1N hydrochloric acid
  5. customdrying under high vacuum

출처 및 근거

ORD 기록
ord-a8d840fed1424d9bb844699d6403cd9f
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07977485B2

반응 노트

불러오는 중…