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

HRID 15469Notes

Reaction equation

HRID 15469 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-56dbd952bc1b4f82975548622247368b
Source dataset
uspto-grants-2010_06
Patent number
US07732477B2

Reaction notes

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