Diisopropylethylamine → N-(1-Azabicyclo[2.2.2]oct-3-yl)-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

HRID 2179568Notes

Reaction equation

HRID 2179568 reaction equation
[Br: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.[ClH:14].Cl.[NH2:16][C@@H:17]1[CH:22]2[CH2:23][CH2:24][N:19]([CH2:20][CH2:21]2)[CH2:18]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[ClH:14].[N:19]12[CH2:24][CH2:23][CH:22]([CH2:21][CH2:20]1)[CH:17]([NH:16][C:11]([C:8]1[S:9][C:10]3[C:2]([Br:1])=[CH:3][CH:4]=[CH:5][C:6]=3[CH:7]=1)=[O:13])[CH2:18]2

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12494972(R)-(+)-3-Aminoquinuclidine DihydrochlorideHCID 179795837-Bromo-1-benzothiophene-2-carboxylic acid

Product 1

HCID 17982629N-(1-Azabicyclo[2.2.2]oct-3-yl)-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

903.8 mg (3.52 mmol) of 7-bromo-1-benzothiophene-2-carboxylic acid (Example 7A), 700 mg (3.52 mmol) of (R)-3-aminoquinuclidine dihydrochloride, 1604.0 mg (4.22 mmol) of HATU, 1635.7 mg (12.66 mmol) of N,N-diisopropylethylamine and 7.0 ml of DMF are reacted by general method C. The reaction mixture is purified by preparative HPLC. The product is dissolved in a 1:1 mixture of 4 M hydrogen chloride in dioxane and 1N hydrochloric acid and then concentrated and dried under high vacuum. 1087 mg (77% 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 1:1 mixture of 4 M hydrogen chloride in dioxane and 1N hydrochloric acid
  3. concentrationconcentrated
  4. customdried under high vacuum

Sources & evidence

ORD record
ord-9ff04553db9e418799d80a75e70df70a
Source dataset
uspto-grants-2015_06
Patent number
US09067931B2

Reaction notes

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