Isoindoline → N-[4-(3-Piperidin-1-ylpropoxy)-2-trifluoromethyl-benzoyl]isoindoline hydrochloride

HRID 268732Notes

Reaction equation

HRID 268732 reaction equation
[N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([Cl:17])=[O:16])=[C:13]([C:20]([F:23])([F:22])[F:21])[CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:26][NH:25]1.CCN(CC1C=CC=CC=1)CC.C=CC1C=CC=CC=1.C=CC1C=CC(C=C)=CC=1>C(Cl)Cl>[ClH:17].[N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([N:25]3[CH2:26][C:27]4[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:24]3)=[O:16])=[C:13]([C:20]([F:23])([F:22])[F:21])[CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 422478IsoindolineHCID 16212021N-benzyl-N-ethylethanamine;1,4-bis(ethenyl)benzene;styreneHCID 179862554-(3-Piperidin-1-yl-propoxy)-2-trifluoromethyl-benzoyl chloride

Product 1

HCID 68963560N-[4-(3-Piperidin-1-ylpropoxy)-2-trifluoromethyl-benzoyl]isoindoline hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-(3-piperidin-1-yl-propoxy)-2-trifluoromethyl-benzoyl chloride (D6) (150 mg) in DCM (10 ml) was added to isoindoline (0.046 ml) and diethylaminomethyl polystyrene (0.60 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) and then dried at 50° C. under high vacuum for 16 h to yield the title compound (E16) as a beige solid (0.094 g). MS electrospray (+ion) 433 (MH+). 1H NMR δ (DMSO-d6): 9.96 (1H, s), 7.63 (1H, d, J=8.36 Hz), 7.46-7.23 (6H, m), 4.82 (2H, s), 4.47 (2H, s), 4.20 (2H, t, J=5.88 Hz), 3.47 (2H, m), 3.19 (2H, m), 2.87 (2H, m), 2.20 (2H, m), 1.80-1.38 (6H, m).

Workup

  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. dry with materialthe residue co-evaporated with toluene (3×10 ml) and then dried at 50° C. under high vacuum for 16 h

Sources & evidence

ORD record
ord-5ca8697046ac4059bdfe3fd118753dd7
Source dataset
uspto-grants-2008_11
Patent number
US07446103B2

Reaction notes

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