Isoindoline → HCID 17986321, compound

HRID 268740Notes

Reaction equation

HRID 268740 reaction equation
Cl.[Cl:2][C:3]1[CH:11]=[C:10]([O:12][CH2:13][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH:9]=[CH:8][C:4]=1[C:5](Cl)=[O:6].CC[N:24]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:25]C.C=CC1C=CC=CC=1.C=CC1C=CC(C=C)=CC=1.C1C2C(=CC=CC=2)CN1>C(Cl)Cl>[ClH:2].[Cl:2][C:3]1[CH:11]=[C:10]([O:12][CH2:13][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH:9]=[CH:8][C:4]=1[C:5]([N:24]1[CH2:25][C:29]2[C:28](=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:27]1)=[O:6]

Participants

5

Reactant 3

HCID 422478IsoindolineHCID 16212021N-benzyl-N-ethylethanamine;1,4-bis(ethenyl)benzene;styreneHCID 17986293HCID 17986293, compound

Product 1

HCID 17986321HCID 17986321, compoundYield 134.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A stirred mixture of 2-chloro-4-(3-piperidin-1-ylpropoxy)benzoyl chloride hydrochloride (D28) (0.10 g) and diethylaminomethyl polystyrene (3.2 mmol/g, 0.8 g) in DCM (10 ml) at rt was treated with isoindoline (0.031 g) and stirred for 16 h. The reaction mixture was chromatographed directly [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM]. Fractions containing the required product were evaporated, redissolved in DCM, treated with excess hydrogen chloride (1M solution in diethyl ether) and then concentrated. The residue was crystallised from acetone to yield the title compound (E61) as a white solid (0.083 g). MS electrospray (+ion) 399/401 (MH+). 1H NMR δ (DMSO-d6): 9.90 (1H, s), 7.41 (2H, m), 7.28 (3H, m), 7.11 (1H, s), 7.02 (1H, m), 4.83 (2H, s), 4.50 (2H, s), 4.14 (2H, t, J=5.9 Hz), 3.45 (2H, m), 3.25 (2H, m), 2.90 (2H, m), 2.18 (2H, m), 1.87-1.30 (6H, m).

Workup

  1. customThe reaction mixture was chromatographed directly [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM]
  2. additionFractions containing the required product
  3. customwere evaporated
  4. dissolutionredissolved in DCM
  5. additiontreated with excess hydrogen chloride (1M solution in diethyl ether)
  6. concentrationconcentrated
  7. customThe residue was crystallised from acetone

Sources & evidence

ORD record
ord-1bd3a5b18183442e976ee3a8d8d82c0e
Source dataset
uspto-grants-2008_11
Patent number
US07446103B2

Reaction notes

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