6-Aminoquinoline → n-(6-Quinolinyl)quinuclidine-3-carboxamide hydrochloride

HRID 1296780Notes

Reaction equation

HRID 1296780 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.C(N(CC)C(C)C)(C)C.Cl.[N:22]12[CH2:29][CH2:28][CH:25]([CH2:26][CH2:27]1)[CH:24]([C:30]([Cl:32])=[O:31])[CH2:23]2>CN(C=O)C>[ClH:32].[N:8]1[C:9]2[C:4](=[CH:3][C:2]([NH:1][C:30]([CH:24]3[CH:25]4[CH2:28][CH2:29][N:22]([CH2:27][CH2:26]4)[CH2:23]3)=[O:31])=[CH:11][CH:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 113736-AminoquinolineHCID 81531DiisopropylethylamineHCID 126734373-Quinuclidinecarbonyl chloride Hydrochloride

Product 1

HCID 10149725n-(6-Quinolinyl)quinuclidine-3-carboxamide hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

172 mg (1.19 mmol) of 6-aminoquinoline are mixed with 461 mg (3.57 mmol) of N,N-diisopropylethylamine in 3 ml of DMF under argon at 0° C. 250 mg (2.57 mmol) of 3-quinuclidinecarbonyl chloride hydrochloride are dissolved in a little dry DMF and added dropwise to the reaction mixture at 0° C. It is then stirred at room temperature overnight. It is worked up by concentrating and taking up in dichloromethane. The crude product is chromatographed on silica gel 60 (mobile phase: dichloromethane/ethyl acetate 10:1, then dichloromethane/methanol 10:1, 3:1). The product fractions are combined and finally purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water, gradient 1:99→30:70).

Workup

  1. additionadded dropwise to the reaction mixture at 0° C
  2. concentrationby concentrating
  3. customThe crude product is chromatographed on silica gel 60 (mobile phase
  4. customfinally purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water, gradient 1:99→30:70)

Sources & evidence

ORD record
ord-fc776fb3e8584746a568e2d06187f522
Source dataset
uspto-grants-2007_07
Patent number
US07247728B2

Reaction notes

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