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 2179634ノート

反応式

HRID 2179634 の反応式
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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒2 回HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-ee0ae4201d534f3a8d7e367514a98fb7
出典データセット
uspto-grants-2015_06
特許番号
US09067931B2

反応ノート

読み込み中…