Diisopropylethylamine → Encenicline Hydrochloride

HRID 335605Notes

Reaction equation

HRID 335605 reaction equation
[Cl:1][C:2]1[C:10]2[S:9][C:8]([C:11]([OH:13])=O)=[CH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=[N:29][C:24]2[CH:25]=[CH:26][CH:27]=[N:28][C:23]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:38](N(CC)C(C)C)(C)[CH3:39]>CN(C=O)C>[ClH:1].[N:28]12[CH2:27][CH2:26][CH:25]([CH2:38][CH2:39]1)[C@@H:24]([NH:29][C:11]([C:8]1[S:9][C:10]3[C:2]([Cl:1])=[CH:3][CH:4]=[CH:5][C:6]=3[CH:7]=1)=[O:13])[CH2:23]2

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 101982427-Chloro-1-benzothiophene-2-carboxylic acid

Product 1

HCID 46208542Encenicline Hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

176.2 mg (0.83 mmol) of 7-chloro-1-benzothiophene-2-carboxylic acid, 150 mg (0.75 mmol) of R-3-aminoquinuclidine dihydrochloride, 343.7 mg (0.90 mmol) of HATU, 350.5 mg (2.71 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 concentrated. 175.2 mg (65.1% of theory) of the title compound are obtained.

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
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-4a933046206146328cb025ccf559f114
Source dataset
uspto-grants-2014_11
Patent number
US08884017B2

Reaction notes

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