Diisopropylethylamine → N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-3-chloro-6-fluoro-1-benzothiophene-2-carboxamide hydrochloride

HRID 335598Notes

Reaction equation

HRID 335598 reaction equation
[Cl:1][C:2]1[C:6]2[CH:7]=[CH:8][C:9]([F:11])=[CH:10][C:5]=2[S:4][C:3]=1[C:12]([OH:14])=O.CN(C(ON1N=[N:30][C:25]2[CH:26]=[CH:27][CH:28]=[N:29][C:24]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:39](N(CC)C(C)C)(C)[CH3:40]>CN(C=O)C>[ClH:1].[N:29]12[CH2:28][CH2:27][CH:26]([CH2:39][CH2:40]1)[C@H:25]([NH:30][C:12]([C:3]1[S:4][C:5]3[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=3[C:2]=1[Cl:1])=[O:14])[CH2:24]2

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 7503303-Chloro-6-fluorobenzo[b]thiophene-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 10309296N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-3-chloro-6-fluoro-1-benzothiophene-2-carboxamide hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

158 mg (0.69 mmol) of 3-chloro-6-fluoro-1-benzothiophene-2-carboxylic acid, 124 mg (0.62 mmol) of S-3-aminoquinuclidine dihydrochloride, 284.2 mg (0.75 mmol) of HATU, 289.8 mg (2.24 mmol) of N,N-diisopropylethylamine and 3.0 ml of DMF are reacted according to the general procedure (variant B). The reaction mixture is purified by preparative HPLC. The product is dissolved in a mixture of 4M HCl in dioxane and methanol and then reconcentrated. 190.5 mg (81.5% of theory) of the title compound are obtained. The analytical data correspond to those of the enantiomeric compound from example 56.

Workup

  1. customThe reaction mixture is purified by preparative HPLC
  2. dissolutionThe product is dissolved in a mixture of 4M HCl in dioxane and methanol

Sources & evidence

ORD record
ord-51ea354fee5a42b38e1da86aef539c32
Source dataset
uspto-grants-2014_11
Patent number
US08884017B2

Reaction notes

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