Sodium Carbonate → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-{3-[(2,2-dimethylpropanoyl)amino]phenyl}-1-benzothiophene-2-carboxamide hydrochloride

HRID 1012760노트

반응식

HRID 1012760 반응식
Br[C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])[CH:5]=[CH:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[ClH:38].[N:39]12[CH2:46][CH2:45][CH:42]([CH2:43][CH2:44]1)[C@@H:41]([NH:47][C:48]([C:50]1[S:51][C:52]3[C:58](Br)=[CH:57][CH:56]=[CH:55][C:53]=3[CH:54]=1)=[O:49])[CH2:40]2.C(=O)([O-])[O-].[Na+].[Na+]>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:38].[N:39]12[CH2:44][CH2:43][CH:42]([CH2:45][CH2:46]1)[C@@H:41]([NH:47][C:48]([C:50]1[S:51][C:52]3[C:58]([C:2]4[CH:7]=[CH:6][CH:5]=[C:4]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])[CH:3]=4)=[CH:57][CH:56]=[CH:55][C:53]=3[CH:54]=1)=[O:49])[CH2:40]2

참가 물질

8

반응물 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 4461573N-(3-bromophenyl)-2,2-dimethylpropanamideHCID 66904832N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

생성물 1

HCID 67313560N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-{3-[(2,2-dimethylpropanoyl)amino]phenyl}-1-benzothiophene-2-carboxamide hydrochloride

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매2회HCID 6228Dimethylformamide용매

실험 절차

143.5 mg (0.56 mmol) of N-(3-bromophenyl)-2,2-dimethylpropanamide, 142.2 mg (0.56 mmol) of bis(pinacolato)diboron, 119.1 mg (1.21 mmol) of potassium acetate, 13.7 mg (0.02 mmol) of PdCl2(dppf), 150.0 mg (0.37 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 8A), 0.93 ml of 2 M sodium carbonate solution and a further 13.7 mg (0.02 mmol) of PdCl2(dppf) in 2.0 ml of DMF are reacted by general method D. An initial purification by preparative HPLC is followed by column chromatography on silica gel (mobile phase: dichloromethane/methanol/ammonia 90:9:1). Drying under high vacuum results in 32.4 mg (17% of theory) of the title compound.

후처리

  1. customAn initial purification by preparative HPLC
  2. customDrying under high vacuum

출처 및 근거

ORD 기록
ord-199c37fad0ce4635913abaf724db6b43
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07977485B2

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