Diisopropylethylamine → Encenicline enantiomer

HRID 15477Notes

Reaction equation

HRID 15477 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-5ad3a80420d04cf4893520c871231748
Source dataset
uspto-grants-2010_06
Patent number
US07732477B2

Reaction notes

Loading…