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

HRID 1012758Notes

Reaction equation

HRID 1012758 reaction equation
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

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-ae8d2fcd9cc140bda25cf167ea411e63
Source dataset
uspto-grants-2011_07
Patent number
US07977485B2

Reaction notes

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