Sodium Carbonate → HCID 86606711, compound

HRID 2179590Notes

Reaction equation

HRID 2179590 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[CH:21]=[C:20](Br)[CH:19]=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2.[CH:23]([C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1)=[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[CH:21]=[C:20]([C:29]4[CH:28]=[CH:27][CH:26]=[C:25]([CH:23]=[O:24])[CH:30]=4)[CH:19]=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343563-Formylphenylboronic acidHCID 66904783HCID 66904783, compound

Product 1

HCID 86606711HCID 86606711, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

200 mg (0.50 mmol) of N-[(3R)-azabicyclo[2.2.2]oct-3-yl]-6-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 11A) and 74.6 mg (0.50 mmol) of 3-formylphenylboronic acid are introduced into 1 ml of DMF. Addition of 0.75 ml of 2 M sodium carbonate solution and 20.3 mg (0.02 mmol) of PdCl2(dppf) is followed by heating to 80° C. After 18 h, the reaction mixture is filtered through kieselguhr and purified by preparative HPLC. The product fractions are concentrated, mixed with a 5:1 mixture of methanol and 4N hydrogen chloride in dioxane and again concentrated. Drying under high vacuum results in 92.4 mg (39.5% of theory) of the title compound.

Workup

  1. filtrationthe reaction mixture is filtered through kieselguhr
  2. custompurified by preparative HPLC
  3. concentrationThe product fractions are concentrated
  4. additionmixed with a 5:1 mixture of methanol and 4N hydrogen chloride in dioxane
  5. concentrationagain concentrated
  6. customDrying under high vacuum

Sources & evidence

ORD record
ord-e317c845f0a14108a18bcbb77b826651
Source dataset
uspto-grants-2015_06
Patent number
US09067931B2

Reaction notes

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