5-fluoro-2,3-dihydro-1H-isoindole hydrochloride → N-[4-(3-Piperidin-1-ylpropoxy)-benzoyl]-5-fluoroisoindoline hydrochloride

HRID 268730Notes

Reaction equation

HRID 268730 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH2:8][NH:7][CH2:6]2.Cl.[N:13]1([CH2:19][CH2:20][CH2:21][O:22][C:23]2[CH:31]=[CH:30][C:26]([C:27]([Cl:29])=[O:28])=[CH:25][CH:24]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1>C(Cl)Cl>[ClH:29].[N:13]1([CH2:19][CH2:20][CH2:21][O:22][C:23]2[CH:24]=[CH:25][C:26]([C:27]([N:7]3[CH2:6][C:5]4[C:9](=[CH:10][CH:11]=[C:3]([F:2])[CH:4]=4)[CH2:8]3)=[O:28])=[CH:30][CH:31]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

4

Reactant 2

HCID 179862865-fluoro-2,3-dihydro-1H-isoindole hydrochlorideHCID 218520624-(3-Piperidin-1-ylpropoxy)benzoyl chloride hydrochloride

Product 1

HCID 17986281N-[4-(3-Piperidin-1-ylpropoxy)-benzoyl]-5-fluoroisoindoline hydrochlorideYield 27.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A stirred mixture of 5-fluoroisoindoline hydrochloride (D8) (183 mg) and diethylaminoethylpolystyrene (626 mg, 3.2 mmol/g) in DCM (10 ml) at rt was treated with 4-(3-piperidin-1-ylpropoxy)-benzoyl chloride hydrochloride (223 mg) (D3). After 1 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 (4M solution in dioxan) and then evaporated. The residue was triturated with acetone, filtered, washed with acetone and dried to yield the title compound (E11) (80 mg). MS electrospray (+ion) 383 (MH+). 1H NMR δ (DMSO-d6): 10.21 (1H, s), 7.61 (2H, d, J=8.8 Hz), 7.05-7.50 (3H, m), 7.01 (2H, d, J=8.8 Hz), 4.81 (4H, m), 4.13. (2H, t, J=6 Hz), 3.46 (2H, m), 3.15 (2H, m), 2.88 (2H, m), 2.21 (2H, m), 1.28-1.92 (6H, m).

Workup

  1. customAfter 1 h the 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 (4M solution in dioxan)
  6. customevaporated
  7. customThe residue was triturated with acetone
  8. filtrationfiltered
  9. washwashed with acetone
  10. customdried

Sources & evidence

ORD record
ord-0f90194842b7439cafe6890eef33d238
Source dataset
uspto-grants-2008_11
Patent number
US07446103B2

Reaction notes

Loading…