Sodium Carbonate → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[4-(4-morpholinylcarbonyl)phenyl]-1-benzothiophene-2-carboxamide hydrochloride

HRID 1012758ノート

反応式

HRID 1012758 の反応式
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[O:14])=[CH:9][CH:8]=1)(=O)=O.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[ClH:46].[N:47]12[CH2:54][CH2:53][CH:50]([CH2:51][CH2:52]1)[C@@H:49]([NH:55][C:56]([C:58]1[S:59][C:60]3[C:66](Br)=[CH:65][CH:64]=[CH:63][C:61]=3[CH:62]=1)=[O:57])[CH2:48]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:46].[N:47]12[CH2:52][CH2:51][CH:50]([CH2:53][CH2:54]1)[C@@H:49]([NH:55][C:56]([C:58]1[S:59][C:60]3[C:66]([C:7]4[CH:8]=[CH:9][C:10]([C:13]([N:15]5[CH2:16][CH2:17][O:18][CH2:19][CH2:20]5)=[O:14])=[CH:11][CH:12]=4)=[CH:65][CH:64]=[CH:63][C:61]=3[CH:62]=1)=[O:57])[CH2:48]2

参加物

8

反応物 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 179828654-(4-Morpholinylcarbonyl)phenyl trifluoromethanesulphonateHCID 66904832N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

生成物 1

HCID 67314168N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[4-(4-morpholinylcarbonyl)phenyl]-1-benzothiophene-2-carboxamide hydrochloride

試薬・触媒・溶媒 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒2 回HCID 6228Dimethylformamide溶媒

実験手順

164.7 mg (0.49 mmol) of 4-(4-morpholinylcarbonyl)phenyl trifluoromethane-sulphonate (Example 18A), 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 2.5 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 24.8 mg (13% 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-ae8d2fcd9cc140bda25cf167ea411e63
出典データセット
uspto-grants-2011_07
特許番号
US07977485B2

反応ノート

読み込み中…