N-benzyl-N-ethylethanamine;1,4-bis(ethenyl)benzene;styrene → N-{2-Chloro-4-[(1-isopropyl-4-piperidinyl)oxy]benzoyl}-5-fluoro-isoindoline hydrochloride

HRID 268742Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 268742
Cl.[Cl:2][C:3]1[CH:11]=[C:10]([O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH:19]([CH3:21])[CH3:20])[CH2:15][CH2:14]2)[CH:9]=[CH:8][C:4]=1[C:5](Cl)=[O:6].CCN(CC1C=CC=CC=1)CC.C=CC1C=CC=CC=1.C=CC1C=CC(C=C)=CC=1.Cl.[F:53][C:54]1[CH:55]=[C:56]2[C:60](=[CH:61][CH:62]=1)[CH2:59][NH:58][CH2:57]2>C(Cl)Cl>[ClH:2].[Cl:2][C:3]1[CH:11]=[C:10]([O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH:19]([CH3:21])[CH3:20])[CH2:15][CH2:14]2)[CH:9]=[CH:8][C:4]=1[C:5]([N:58]1[CH2:57][C:56]2[C:60](=[CH:61][CH:62]=[C:54]([F:53])[CH:55]=2)[CH2:59]1)=[O:6]

Komponenten

5

Edukt 3

HCID 16212021N-benzyl-N-ethylethanamine;1,4-bis(ethenyl)benzene;styreneHCID 179862865-fluoro-2,3-dihydro-1H-isoindole hydrochlorideHCID 179862952-Chloro-4-[(1-isopropyl-4-piperidinyl)oxy]benzoyl chloride hydrochloride

Produkt 1

HCID 17986277N-{2-Chloro-4-[(1-isopropyl-4-piperidinyl)oxy]benzoyl}-5-fluoro-isoindoline hydrochlorideAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A stirred mixture of 2-chloro-4-[(1-isopropyl-4-piperidinyl)oxy]benzoyl chloride hydrochloride (D33) (0.20 g) and diethylaminomethyl polystyrene (3.2 mmol/g, 1.0 g) in DCM (10 ml) at rt was treated with 5-fluoroisoindoline hydrochloride (D8) (0.10 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 (E63) as a white solid (0.09 g). MS electrospray (+ion) 417/419 (MH+). 1H NMR δ (DMSO-d6): 9.80 (1H, s), 7.22-6.81 (6H, m), 4.70-4.39 (3H, m), 4.25 (3H, m), 3.24 (2H, m), 2.88 (2H, m), 2.10-1.70 (4H, m), 1.06 (6H, m).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-929a51ba2232440f937c281627b27007
Quelldatensatz
uspto-grants-2008_11
Patentnummer
US07446103B2

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