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

HRID 1012772
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HRID 1012772 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:36]=[CH:35][CH:34]=[CH:33][C:32]=1B(O)O>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:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[O:30][CH3:29])=[CH:26][CH:25]=[CH:24][C:22]=3[CH:23]=1)=[O:18])[CH2:9]2
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참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 67313990N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

생성물 1

HCID 67314260N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-7-(2-methoxyphenyl)-1-benzothiophene-2-carboxamide hydrochloride

시약·촉매·용매 2

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
촉매
HCID 6228Dimethylformamide용매

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온도
70 °C

실험 절차

0.67 ml of 2 M sodium carbonate solution and 18.3 mg (0.02 mmol) of PdCl2(dppf) are added to a mixture of 200 mg (0.45 mmol) of N-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 22A) and 68.1 mg (0.45 mmol) of 2-methoxyphenylboronic acid in 2 ml of DMF. The reaction mixture is heated at 70° C. for 17 h and, after cooling, filtered through kieselguhr and purified by preparative HPLC. The product fractions are concentrated, taken up in a 5:1 mixture of methanol and 1N hydrochloric acid and again concentrated. Drying under high vacuum results in 112 mg (588% of theory) of the title compound.

후처리

  1. temperatureafter cooling
  2. filtrationfiltered through kieselguhr
  3. custompurified by preparative HPLC
  4. concentrationThe product fractions are concentrated
  5. additiontaken up in a 5:1 mixture of methanol and 1N hydrochloric acid
  6. concentrationagain concentrated
  7. customDrying under high vacuum

출처 및 근거

ORD 기록
ord-eeba1ffcc8314ce6951c9a35fc87e61e
출처 데이터셋
uspto-grants-2011_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07977485B2

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