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

HRID 2179606
Notes
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Reaction equation

HRID 2179606 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.[C:29]1(B(O)O)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=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:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:26][CH:25]=[CH:24][C:22]=3[CH:23]=1)=[O:18])[CH2:9]2
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 66904832N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

Product 1

HCID 67313857N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-phenyl-1-benzothiophene-2-carboxamide hydrochloride

Reagents, catalysts & solvents 2

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
Catalyst
2×
HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

0.14 ml of 2M aqueous sodium carbonate solution and 5.7 mg (0.007 mmol) of PdCl2(dppf) are added to a mixture of 56mg (0.14 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 8A) and 18.7 mg (0.15 mmol) of phenylboronic acid in 1 ml of DMF. The reaction mixture is heated to 80° C. After 3 h at this temperature, a further 5.7 mg (0.007 mmol) of PdCl2(dppf) are added, and the mixture is stirred at 80° C. for a further 12 h. The reaction mixture is filtered through kieselguhr and evaporated to dryness. Purification of the crude product by preparative HPLC, subsequent addition of 1N hydrochloric acid and drying under high vacuum result in 10.6 mg (18% of theory) of the title compound.

Workup

  1. filtrationThe reaction mixture is filtered through kieselguhr
  2. customevaporated to dryness
  3. customPurification of the crude product
  4. additionby preparative HPLC, subsequent addition of 1N hydrochloric acid
  5. customdrying under high vacuum

Sources & evidence

ORD record
ord-756c47f121f94f50b3d311bc7de9cb7a
Source dataset
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09067931B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes