Diisopropylethylamine → Encenicline enantiomer

HRID 335606Notes

Reaction equation

HRID 335606 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 68431081Encenicline enantiomer

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 S-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. 231.9 mg (85.7% of theory) of the title compound are obtained. The analytical data correspond to those of the enantiomeric compound from example 69.

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-e5cd8f77bd804c99bdc08f8b077fc880
Source dataset
uspto-grants-2014_11
Patent number
US08884017B2

Reaction notes

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