Triphenylphosphine → tert-Butyl (2S,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-[({4-[3-chloro-4-fluoro-anilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate

HRID 1443014Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1443014
CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C.[Cl:17][C:18]1[CH:19]=[C:20]([CH:35]=[CH:36][C:37]=1[F:38])[NH:21][C:22]1[C:31]2[C:30]([OH:32])=[CH:29][C:28]([O:33][CH3:34])=[CH:27][C:26]=2[N:25]=[CH:24][N:23]=1.[Si:39]([O:46][C@@H:47]1[CH2:51][N:50]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C@H:49]([CH2:59]O)[CH2:48]1)([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Si:39]([O:46][C@@H:47]1[CH2:51][N:50]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C@H:49]([CH2:59][O:32][C:30]2[CH:29]=[C:28]([O:33][CH3:34])[CH:27]=[C:26]3[C:31]=2[C:22]([NH:21][C:20]2[CH:35]=[CH:36][C:37]([F:38])=[C:18]([Cl:17])[CH:19]=2)=[N:23][CH:24]=[N:25]3)[CH2:48]1)([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40]

Komponenten

6

Edukt 4

HCID 11776TriphenylphosphineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 58303448tert-butyl (2S,4S)-4-[tert-butyl(dimethyl)silyl]oxy-2-(hydroxymethyl)pyrrolidine-1-carboxylateHCID 1363475184-[3-Chloro-4-fluoroanilino]-7-methoxyquinazolin-5-ol

Produkt 1

HCID 86607808tert-Butyl (2S,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-[({4-[3-chloro-4-fluoro-anilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylateAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Di-tert-butylazodicarboxylate (DTAD, 1.38 g) was added in one portion to a mixture of 4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-ol (1.28 g), tert-butyl (2S,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-(hydroxymethyl)-pyrrolidine-1-carboxylate (1.66 g), and triphenylphosphine (1.58 g) in DCM (100 ml) at room temperature, under an atmosphere of nitrogen. The reaction mixture was stirred at room temperature for 28 hours and then concentrated in vacuo to leave a brown oil. Purification by column chromatography, using 0-50% ethyl acetate in hexane as eluent, gave tert-butyl (2S,4S)-4-{[tert-butyl(dimethyl)silyl]-oxy}-2-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]-pyrrolidine-1-carboxylate as a white solid (1.13 g, 45%); Mass spectrum MH+ 633.

Aufarbeitung

  1. concentrationconcentrated in vacuo
  2. customto leave a brown oil
  3. customPurification by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-2d638cd08e944adc95d1078b1e15a5b4
Quelldatensatz
uspto-grants-2010_02
Patentnummer
US07659279B2

Notizen zur Reaktion

Wird geladen…