Sodium Carbonate → HCID 67312996, compound

HRID 2179639Notes

Reaction equation

HRID 2179639 reaction equation
[ClH:1].[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C@@H:4]([NH:10][C:11]([C:13]1[S:14][C:15]3[C:21](Br)=[CH:20][CH:19]=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2.[NH2:23][C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+]>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].CN(C=O)C>[ClH:1].[NH2:23][C:24]1[CH:29]=[C:28]([C:21]2[C:15]3[S:14][C:13]([C:11]([NH:10][C@@H:4]4[CH:5]5[CH2:8][CH2:9][N:2]([CH2:7][CH2:6]5)[CH2:3]4)=[O:12])=[CH:17][C:16]=3[CH:18]=[CH:19][CH:20]=2)[CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 922693-Aminophenylboronic acidHCID 66904832N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

Product 1

HCID 67312996HCID 67312996, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
60 °C

Procedure

200 mg (0.50 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 8A) and 68.2 mg (0.50 mmol) of 3-aminophenylboronic acid are introduced into 1.5 ml of DMF. Addition of 0.78 ml of 2 M sodium carbonate solution and 20.3 mg (0.02 mmol) of PdCl2(dppf) is followed by heating at 60° C. for 18 h. After cooling, the reaction mixture is filtered through kieselguhr and purified by separation by preparative HPLC. The product fractions are concentrated and, after addition of a 3:1 mixture of acetonitrile and 1N hydrochloric acid, again concentrated. Drying under high vacuum results in 201 mg (98% of theory) of the title compound.

Workup

  1. temperatureAfter cooling
  2. filtrationthe reaction mixture is filtered through kieselguhr
  3. custompurified by separation by preparative HPLC
  4. concentrationThe product fractions are concentrated
  5. additionafter addition of a 3:1 mixture of acetonitrile and 1N hydrochloric acid
  6. concentrationagain concentrated
  7. customDrying under high vacuum

Sources & evidence

ORD record
ord-d70c3584b413484081d18ed515269a75
Source dataset
uspto-grants-2015_06
Patent number
US09067931B2

Reaction notes

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