Sodium Carbonate → HCID 67313922, compound

HRID 1012738Notes

Reaction equation

HRID 1012738 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.[O:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=2)[CH2:25][CH2:24]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].[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:32]4[CH:31]=[CH:30][C:29]([N:26]5[CH2:25][CH2:24][O:23][CH2:28][CH2:27]5)=[CH:34][CH:33]=4)[CH:19]=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2

Participants

6

Reactant 3

HCID 10340Sodium Carbonate2×HCID 2795359(4-(Morpholin-4-yl)phenyl)boronic acid2×HCID 66904783HCID 66904783, compound

Product 1

HCID 67313922HCID 67313922, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

100 mg (0.25 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 11A) and 51.5 mg (0.25 mmol) of 4-morpholinophenylboronic acid are introduced into 1 ml of DMF. Addition of 0.37 ml of 2 M sodium carbonate solution and 10.2 mg (0.01 mmol) of PdCl2(dppf) is followed by heating to 80° C. After 16 h, a further 51.5 mg (0.25 mmol) of 4-morpholinophenylboronic acid, 0.37 ml of 2 M sodium carbonate solution and 10.2 mg (0.01 mmol) of PdCl2(dppf) are added. The mixture is heated at 80° C. for a further 4 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 5:1 mixture of methanol and 4 M hydrogen chloride in dioxane, again concentrated. Drying under high vacuum results in 83 mg (69% of theory) of the title compound.

Workup

  1. temperatureThe mixture is heated at 80° C. for a further 4 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 5:1 mixture of methanol and 4 M hydrogen chloride in dioxane
  7. concentrationagain concentrated
  8. customDrying under high vacuum

Sources & evidence

ORD record
ord-1d63f8bd77ce4ea699528c78fee65f8f
Source dataset
uspto-grants-2011_07
Patent number
US07977485B2

Reaction notes

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