Phthalimide → tert-butyl 4-(1-(4-chlorophenyl)-3-(1,3-dioxoisoindolin-2-yl)propylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate

HRID 423056Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 423056
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]1(=[O:30])[NH:24][C:23](=[O:25])[C:22]2=[CH:26][CH:27]=[CH:28][CH:29]=[C:21]12.[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([CH:38]([NH:42][C:43]([C:45]2([NH:60][C:61](=[O:67])[O:62][C:63]([CH3:66])([CH3:65])[CH3:64])[CH2:50][CH2:49][N:48]([C:51]3[C:52]4[CH:59]=[CH:58][NH:57][C:53]=4[N:54]=[CH:55][N:56]=3)[CH2:47][CH2:46]2)=[O:44])[CH2:39][CH2:40]O)=[CH:34][CH:33]=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[Cl:31][C:32]1[CH:33]=[CH:34][C:35]([CH:38]([NH:42][C:43]([C:45]2([NH:60][C:61](=[O:67])[O:62][C:63]([CH3:66])([CH3:65])[CH3:64])[CH2:46][CH2:47][N:48]([C:51]3[C:52]4[CH:59]=[CH:58][NH:57][C:53]=4[N:54]=[CH:55][N:56]=3)[CH2:49][CH2:50]2)=[O:44])[CH2:39][CH2:40][N:24]2[C:20](=[O:30])[C:21]3[C:22](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:23]2=[O:25])=[CH:36][CH:37]=1

Komponenten

6

Edukt 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 57750387tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate2×

Produkt 1

HCID 57750333tert-butyl 4-(1-(4-chlorophenyl)-3-(1,3-dioxoisoindolin-2-yl)propylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamateAusbeute 21,23 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Triphenylphosphine (158 mg) and phthalimide (22.11 mg) were added in one portion to a stirred solution of tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (Intermediate 36) (53 mg) dissolved in THF (10 mL) and cooled to 0° C. under argon. The resulting solution was stirred at 0° C. for 30 minutes. Diethyl azodicarboxylate (0.093 mL) was added dropwise at 0° C. under argon. The resulting suspension was stirred at 0° C. for 60 minutes and overnight at room temperature. The suspension was quenched with water. The THF was removed in vacuo and the aqueous phase extracted with DCM. The organic phase was dried and concentrated to provide crude product. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% methanol in DCM. The solvent was evaporated to dryness to afford tert-butyl 4-(1-(4-chlorophenyl)-3-(1,3-dioxoisoindolin-2-yl)propylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate as a white solid (14.00 mg, 21.23%).

Aufarbeitung

  1. stirringThe resulting suspension was stirred at 0° C. for 60 minutes and overnight at room temperature
  2. customThe suspension was quenched with water
  3. customThe THF was removed in vacuo
  4. extractionthe aqueous phase extracted with DCM
  5. customThe organic phase was dried
  6. concentrationconcentrated
  7. customto provide crude product
  8. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 10% methanol in DCM
  9. customThe solvent was evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-1a88c7fb38774fa2a7b7c864b3e52e87
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08101623B2

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