Sodium Carbonate → HCID 67314106, compound

HRID 2179635Notes

Reaction equation

HRID 2179635 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.[C:23]([C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1)([OH:25])=[O:24].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].[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]([C:30]4[CH:31]=[C:26]([CH:27]=[CH:28][CH:29]=4)[C:23]([OH:25])=[O:24])=[CH:20][CH:19]=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27339573-Carboxyphenylboronic acidHCID 66904832N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

Product 1

HCID 67314106HCID 67314106, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 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 82.6 mg (0.50 mmol) of 3-carboxyphenylboronic 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. After 18 h, a further 20.3 mg (0.02 mmol) of PdCl2(dppf) are added, and the mixture is heated at 90° C. for a further 18 h. After cooling, the reaction mixture is filtered through kieselguhr and purified 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 103 mg (45% of theory) of the title compound.

Workup

  1. temperaturethe mixture is heated at 90° C. for a further 18 h
  2. temperatureAfter cooling
  3. filtrationthe reaction mixture is filtered through kieselguhr
  4. custompurified by preparative HPLC
  5. concentrationThe product fractions are concentrated
  6. additionafter addition of a 3:1 mixture of acetonitrile and 1N hydrochloric acid
  7. concentrationagain concentrated
  8. customDrying under high vacuum

Sources & evidence

ORD record
ord-8a6403925c6d44ed8fc30d89db65cb7d
Source dataset
uspto-grants-2015_06
Patent number
US09067931B2

Reaction notes

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