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

HRID 2179627Notes

Reaction equation

HRID 2179627 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[ClH:44].[N:45]12[CH2:52][CH2:51][CH:48]([CH2:49][CH2:50]1)[C@@H:47]([NH:53][C:54]([C:56]1[S:57][C:58]3[C:64](Br)=[CH:63][CH:62]=[CH:61][C:59]=3[CH:60]=1)=[O:55])[CH2:46]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:44].[ClH:44].[N:45]12[CH2:50][CH2:49][CH:48]([CH2:51][CH2:52]1)[C@@H:47]([NH:53][C:54]([C:56]1[S:57][C:58]3[C:64]([C:2]4[CH:3]=[CH:4][C:5]([N:8]5[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]5)=[CH:6][CH:7]=4)=[CH:63][CH:62]=[CH:61][C:59]=3[CH:60]=1)=[O:55])[CH2:46]2

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 11824027Tert-butyl 4-(4-bromophenyl)piperazine-1-carboxylateHCID 66904832N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

Product 1

HCID 67313590N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[4-(1-piperazinyl)phenyl]-1-benzothiophene-2-carboxamide dihydrochloride

Reagents, catalysts & solvents 2

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

Procedure

165.6 mg (0.49 mmol) of tert-butyl 4-(4-bromophenyl)-1-piperazinecarboxylate, 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 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 ml of DMF are reacted by general method D. The compound purified by preparative HPLC is dissolved in 3 ml of methanol and, after addition of 3 ml of 4 M hydrogen chloride in dioxane, stirred at room temperature for 30 min. The contents of the flask are concentrated in vacuo, and the residue is azeotropically distilled with toluene twice. Drying under high vacuum results in 54 mg (28% of theory) of the title compound.

Workup

  1. customThe compound purified by preparative HPLC
  2. dissolutionis dissolved in 3 ml of methanol
  3. additionafter addition of 3 ml of 4 M hydrogen chloride in dioxane
  4. concentrationThe contents of the flask are concentrated in vacuo
  5. distillationthe residue is azeotropically distilled with toluene twice
  6. customDrying under high vacuum

Sources & evidence

ORD record
ord-4b4a72c394664babbb6831f46dcd7caf
Source dataset
uspto-grants-2015_06
Patent number
US09067931B2

Reaction notes

Loading…