1-Hydroxybenzotriazole → rac-N-(1-Azabicyclo[2.2.2]oct-3-yl)-5-nitro-1-benzothiophene-2-carboxamide hydrochloride

HRID 658182Notes

Reaction equation

HRID 658182 reaction equation
CN(C([O:8][N:9]1N=N[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C1C=CC2N([OH:32])N=NC=2C=1.[ClH:33].Cl.[NH2:35][CH:36]1[CH:41]2[CH2:42][CH2:43][N:38]([CH2:39][CH2:40]2)[CH2:37]1.[N+](C1[S:51][C:50]([C:52](O)=[O:53])=[CH:49]C=1)([O-])=O.C(N(C(C)C)CC)(C)C>CN(C=O)C>[ClH:33].[N:38]12[CH2:43][CH2:42][CH:41]([CH2:40][CH2:39]1)[CH:36]([NH:35][C:52]([C:50]1[S:51][C:13]3[CH:12]=[CH:11][C:10]([N+:9]([O-:8])=[O:32])=[CH:15][C:14]=3[CH:49]=1)=[O:53])[CH2:37]2

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 805915-Nitro-2-thenoic acidHCID 81531DiisopropylethylamineHCID 197853Quinuclidine, 3-amino-, dihydrochlorideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate

Product 1

HCID 10193833rac-N-(1-Azabicyclo[2.2.2]oct-3-yl)-5-nitro-1-benzothiophene-2-carboxamide hydrochlorideYield 48.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

At RT, initially 244 mg (0.76 mmol) of TBTU and 104 mg (0.78 mmol) of HOBt followed by 153 mg (0.77 mmol) of 3-aminoquinuclidine dihydrochloride are added to a solution of 180 mg (0.81 mmol) of 5-nitrothiophene-2-carboxylic acid and diisopropylethylamine (0.8 ml) in 4 ml of DMF. The mixture is stirred at RT for 4 h. For work-up, the mixture is concentrated and the residue is taken up in a mixture of chloroform and excess aqueous sodium hydroxide solution. The phases are separated and the aqueous phase is repeatedly re-extracted with chloroform. The combined organic phases are dried over sodium sulfate and concentrated, and the crude product is chromatographed on silica gel (mobile phase: chloroform/methanol/conc. ammonia 100:5:0.5→100:20:2). The resulting product is taken up in THF, excess HCl in diethyl ether is added, then the mixture is concentrated and the product is dried under high vacuum. 136 mg (47% of theory) of the hydrochloride are obtained.

Workup

  1. customAt RT
  2. concentrationFor work-up, the mixture is concentrated
  3. additionthe residue is taken up in a mixture of chloroform and excess aqueous sodium hydroxide solution
  4. customThe phases are separated
  5. extractionthe aqueous phase is repeatedly re-extracted with chloroform
  6. dry with materialThe combined organic phases are dried over sodium sulfate
  7. concentrationconcentrated
  8. customthe crude product is chromatographed on silica gel (mobile phase: chloroform/methanol/conc. ammonia 100:5:0.5→100:20:2)
  9. additionexcess HCl in diethyl ether is added
  10. concentrationthe mixture is concentrated
  11. customthe product is dried under high vacuum

Sources & evidence

ORD record
ord-52a6f5fb8b5141e0a5f2bd5f90385955
Source dataset
uspto-grants-2011_12
Patent number
US08076355B2

Reaction notes

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