7-Cyano-1,2,3,4-tetrahydroisoquinoline → N-[4-(3-Piperidin-1-ylpropoxy)benzoyl]-7-cyano-1,2,3,4-tetrahydroisoquinoline hydrochloride

HRID 268734

Reaktionsgleichung

Reaktionsgleichung von HRID 268734
Cl.[N:2]1([CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:20]=[CH:19][C:15]([C:16]([Cl:18])=[O:17])=[CH:14][CH:13]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[C:21]([C:23]1[CH:32]=[C:31]2[C:26]([CH2:27][CH2:28][NH:29][CH2:30]2)=[CH:25][CH:24]=1)#[N:22].CCN(CC1C=CC=CC=1)CC.C=CC1C=CC=CC=1.C=CC1C=CC(C=C)=CC=1>C(Cl)Cl>[ClH:18].[N:2]1([CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:20]=[CH:19][C:15]([C:16]([N:29]3[CH2:28][CH2:27][C:26]4[C:31](=[CH:32][C:23]([C:21]#[N:22])=[CH:24][CH:25]=4)[CH2:30]3)=[O:17])=[CH:14][CH:13]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1

Komponenten

5

Edukt 3

HCID 101762437-Cyano-1,2,3,4-tetrahydroisoquinolineHCID 16212021N-benzyl-N-ethylethanamine;1,4-bis(ethenyl)benzene;styreneHCID 218520624-(3-Piperidin-1-ylpropoxy)benzoyl chloride hydrochloride

Produkt 1

HCID 17986288N-[4-(3-Piperidin-1-ylpropoxy)benzoyl]-7-cyano-1,2,3,4-tetrahydroisoquinoline hydrochlorideAusbeute 15,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of 4-(3-piperidin-1-ylpropoxy)benzoyl chloride hydrochloride (D3) (0.14 g) in DCM (10 ml) was added to 7-cyano-1,2,3,4-tetrahydroisoquinoline (WO98/50364) (0.08 g) and diethylaminomethyl polystyrene (0.6 g, 3.2 mmol/g). The mixture was stirred for 16 h then loaded directly onto a silica column and eluted with 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM. The isolated free base was dissolved in DCM (5 ml) and treated with 4N HCl/dioxane solution (1 ml) with stirring for 10 min. The mixture was concentrated and the residue co-evaporated with toluene (3×10 ml) then crystallised from ethanol/diethyl ether, and dried at 80° C. under high vacuum for 16 h to yield the title compound (E18) as a beige solid (0.03 g). MS electrospray (+ion) 404 (MH+). 1H NMR δ (DMSO-d6): 9.91 (1H, s), 7.85 (1H, m), 7.65 (1H, d, J=7.9 Hz), 7.42 (3H, m), 7.02 (2H, d, J=8.6), 4.73 (2H, s), 4.11 (2H, t, J=5.9 Hz), 3.68 (2H, m), 3.44 (2H, m), 3.17 (2H, m), 2.93 (4H, m), 2.20 (2H, m), 1.91-1.41 (6H, m).

Aufarbeitung

  1. washeluted with 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM
  2. dissolutionThe isolated free base was dissolved in DCM (5 ml)
  3. additiontreated with 4N HCl/dioxane solution (1 ml)
  4. stirringwith stirring for 10 min
  5. concentrationThe mixture was concentrated
  6. customthe residue co-evaporated with toluene (3×10 ml) then crystallised from ethanol/diethyl ether
  7. customdried at 80° C. under high vacuum for 16 h

Quellen und Nachweise

ORD-Eintrag
ord-98ce81232d224a6391e2e6af01398e95
Quelldatensatz
uspto-grants-2008_11
Patentnummer
US07446103B2

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