Sodium Carbonate → N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-7-(3-methoxyphenyl)-1-benzothiophene-2-carboxamide hydrochloride

HRID 2179643Notes

Reaction equation

HRID 2179643 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[ClH:7].[N:8]12[CH2:15][CH2:14][CH:11]([CH2:12][CH2:13]1)[C@H:10]([NH:16][C:17]([C:19]1[S:20][C:21]3[C:27](Br)=[CH:26][CH:25]=[CH:24][C:22]=3[CH:23]=1)=[O:18])[CH2:9]2.[CH3:29][O:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1>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:7].[N:8]12[CH2:15][CH2:14][CH:11]([CH2:12][CH2:13]1)[C@H:10]([NH:16][C:17]([C:19]1[S:20][C:21]3[C:27]([C:35]4[CH:34]=[CH:33][CH:32]=[C:31]([O:30][CH3:29])[CH:36]=4)=[CH:26][CH:25]=[CH:24][C:22]=3[CH:23]=1)=[O:18])[CH2:9]2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734370(3-Methoxyphenyl)boronic acidHCID 67313990N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

Product 1

HCID 67314512N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-7-(3-methoxyphenyl)-1-benzothiophene-2-carboxamide hydrochloride

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

0.67 ml of 2 M aqueous sodium carbonate solution and 18.3 mg (0.02 mmol) of PdCl2(dppf) are added to a mixture of 200 mg (0.45 mmol) of N-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 22A) and 68.1 mg (0.45 mmol) of 3-methoxyphenylboronic acid in 2 ml of DMF. The reaction mixture is heated at 80° C. for 17 h, filtered through kieselguhr and evaporated to dryness. A purification by preparative HPLC is followed by column chromatography on silica gel (mobile phase: dichloromethane/methanol-/ammonia 90:9:1). The product fractions are concentrated, taken up in a 5:1 mixture of methanol and 1N hydrochloric acid and again concentrated. Drying under high vacuum results in 97.7 mg (48% of theory) of the title compound.

Workup

  1. filtrationfiltered through kieselguhr
  2. customevaporated to dryness
  3. customA purification by preparative HPLC
  4. concentrationThe product fractions are concentrated
  5. additiontaken up in a 5:1 mixture of methanol and 1N hydrochloric acid
  6. concentrationagain concentrated
  7. customDrying under high vacuum

Sources & evidence

ORD record
ord-e76f05c465424f87b039a8cc54a4a007
Source dataset
uspto-grants-2015_06
Patent number
US09067931B2

Reaction notes

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