1,2-Dichloroethane → N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

HRID 1012706Notes

Reaction equation

HRID 1012706 reaction equation
C(Cl)C[Cl:3].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[Br:22][C:23]1[C:31]2[S:30][C:29]([C:32]([OH:34])=O)=[CH:28][C:27]=2[CH:26]=[CH:25][CH:24]=1.Cl.Cl.[NH2:37][C@H:38]1[CH:43]2[CH2:44][CH2:45][N:40]([CH2:41][CH2:42]2)[CH2:39]1.C(=O)(O)[O-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[ClH:3].[N:40]12[CH2:45][CH2:44][CH:43]([CH2:42][CH2:41]1)[C@H:38]([NH:37][C:32]([C:29]1[S:30][C:31]3[C:23]([Br:22])=[CH:24][CH:25]=[CH:26][C:27]=3[CH:28]=1)=[O:34])[CH2:39]2

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 12494973(3S)-1-azabicyclo[2.2.2]octan-3-amine dihydrochlorideHCID 179795837-Bromo-1-benzothiophene-2-carboxylic acid

Product 1

HCID 67313990N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3.58 g (18.7 mmol) of EDC, 2.52 g (18.7 mmol) of HOBt and 7.8 ml (56 mmol) of triethylamine are added to a solution, cooled to 0° C., of 4.0 g (15.6 mmol) of 7-bromo-1-benzothiophene-2-carboxylic acid (Example 7A) and 3.10 g (15.6 mmol) of (S)-3-aminoquinuclidine dihydrochloride in 50 ml of DMF. The mixture is stirred at room temperature for 18 h. The reaction is stopped by adding 10% strength sodium bicarbonate solution. The precipitate resulting after addition of ethyl acetate is filtered off. The aqueous phase is extracted with ethyl acetate, the combined organic phases are dried over sodium sulphate and concentrated, and the residue is dried under high vacuum. 4.70 g (68% of theory) of the title compound are obtained. The spectroscopic data agree with those of the enantiomeric compound (Example 8A).

Workup

  1. customThe precipitate resulting
  2. filtrationis filtered off
  3. extractionThe aqueous phase is extracted with ethyl acetate
  4. dry with materialthe combined organic phases are dried over sodium sulphate
  5. concentrationconcentrated
  6. customthe residue is dried under high vacuum

Sources & evidence

ORD record
ord-8c3f6bdd27eb4d65b2cd2db08a42e94d
Source dataset
uspto-grants-2011_07
Patent number
US07977485B2

Reaction notes

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