Sodium Carbonate → HCID 67313744, compound

HRID 2179620Notes

Reaction equation

HRID 2179620 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[S:30][C:29](B(O)O)=[CH:28][CH:27]=1)(=[O:25])[CH3:24].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].[C:23]([C:26]1[S:30][C:29]([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:28][CH:27]=1)(=[O:25])[CH3:24]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 4143377(5-Acetylthiophen-2-yl)boronic acidHCID 66904832N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

Product 1

HCID 67313744HCID 67313744, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
85 °C

Procedure

100 mg (0.25 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 8A) and 42.3 mg (0.25 mmol) of 5-acetyl-2-thienylboronic acid are introduced into 1.5 ml of DMF. Addition of 0.37 ml of 2 M sodium carbonate solution and 9.11 mg (0.01 mmol) of PdCl2(dppf) is followed by heating to 85° C. After 14 h, the reaction mixture is filtered through kieselguhr and purified by preparative HPLC. The product fractions are concentrated, taken up in a 5:1 mixture of methanol and 1N hydrochloric acid, again concentrated and dried under high vacuum. 52 mg (46% of theory) of the title compound are obtained.

Workup

  1. filtrationthe reaction mixture is filtered through kieselguhr
  2. custompurified by preparative HPLC
  3. concentrationThe product fractions are concentrated
  4. additiontaken up in a 5:1 mixture of methanol and 1N hydrochloric acid
  5. concentrationagain concentrated
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-ba488199d76d46dba09be98b90f4bbaa
Source dataset
uspto-grants-2015_06
Patent number
US09067931B2

Reaction notes

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