N-3-Bromopropylphthalimide → (R)-2-(3-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-yl)propyl)isoindoline-1,3-dione

HRID 2190032Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2190032
Cl.Cl.[Cl:3][C:4]1[CH:5]=[C:6]2[C:12]3([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[CH2:11][N:10]([C:18]3[C:19]4[C@H:26]([CH3:27])[CH2:25][CH2:24][C:20]=4[N:21]=[CH:22][N:23]=3)[C:7]2=[CH:8][CH:9]=1.Br[CH2:29][CH2:30][CH2:31][N:32]1[C:40](=[O:41])[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:33]1=[O:42].CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[C:6]2[C:12]3([CH2:17][CH2:16][N:15]([CH2:29][CH2:30][CH2:31][N:32]4[C:40](=[O:41])[C:39]5[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=5)[C:33]4=[O:42])[CH2:14][CH2:13]3)[CH2:11][N:10]([C:18]3[C:19]4[C@H:26]([CH3:27])[CH2:25][CH2:24][C:20]=4[N:21]=[CH:22][N:23]=3)[C:7]2=[CH:8][CH:9]=1

Komponenten

5

Edukt 3

HCID 21611N-3-BromopropylphthalimideHCID 81531DiisopropylethylamineHCID 68736280(R)-5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]dihydrochloride

Produkt 1

HCID 68764576(R)-2-(3-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-yl)propyl)isoindoline-1,3-dioneAusbeute 63,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

A mixture of (R)-5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]dihydrochloride (15 mg, 0.035 mmol), 2-(3-bromopropyl)isoindoline-1,3-dione (13 mg, 0.049 mmol), DIEA (0.018 mL, 0.11 mmol) and DMF (0.5 mL) was heated at about 150° C. in microwave for about 30 min. After cooling, the reaction mixture was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc. The combined organic layers were washed with water and brine, dried and concentrated. The residue was purified by column chromatography (DCM:MeOH, 20:1) to give (R)-2-(3-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-yl)propyl)isoindoline-1,3-dione (12 mg, 63%). LCMS (APCI+) m/z 542, 544 [M+H]+; Rt=3.79 min.

Aufarbeitung

  1. temperatureAfter cooling
  2. customthe reaction mixture was partitioned between EtOAc and water
  3. extractionThe aqueous phase was extracted with EtOAc
  4. washThe combined organic layers were washed with water and brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (DCM:MeOH, 20:1)

Quellen und Nachweise

ORD-Eintrag
ord-9a8b70679d2f4d248106369597edd5fd
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08324221B2

Notizen zur Reaktion

Wird geladen…