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

HRID 1443001Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1443001
CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C.[Cl:17][C:18]1[CH:19]=[C:20]([NH:25][C:26]2[C:35]3[C:34]([OH:36])=[CH:33][C:32]([O:37][CH3:38])=[CH:31][C:30]=3[N:29]=[CH:28][N:27]=2)[CH:21]=[CH:22][C:23]=1[F:24].[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>[C:42]([Si:39]([CH3:41])([CH3:40])[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:36][C:34]2[CH:33]=[C:32]([O:37][CH3:38])[CH:31]=[C:30]3[C:35]=2[C:26]([NH:25][C:20]2[CH:21]=[CH:22][C:23]([F:24])=[C:18]([Cl:17])[CH:19]=2)=[N:27][CH:28]=[N:29]3)[CH2:48]1)([CH3:44])([CH3:45])[CH3:43]

Komponenten

6

Edukt 4

HCID 11776TriphenylphosphineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 66962096tert-butyl (2R,4S)-4-((tert-butyldimethylsilyl)oxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylateHCID 1363475184-[3-Chloro-4-fluoroanilino]-7-methoxyquinazolin-5-ol

Produkt 1

HCID 86607805tert-butyl (2R,4S)-4-{[tert-butyl-(dimethyl)silyl]-oxy}-2-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]-pyrrolidine-1-carboxylateAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Di-tert-butylazodicarboxylate (DTAD, 623 mg) was added in one portion to a mixture of 4-[(3-chloro-4-fluorophenyl)-amino]-7-methoxy-quinazolin-5-ol (578 mg, prepared as described in Example 1, preparation of starting materials), tert-butyl (2R,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-(hydroxymethyl)pyrrolidine-1-carboxylate (750 mg), and triphenylphosphine (710 mg) in DCM (100 ml) at room temperature, under an atmosphere of nitrogen. The reaction mixture was stirred at room temperature for 24 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 (2R,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 (671 mg, 59%); NMR spectrum (DMSO-d6) 8.46 (s, 1H), 8.03 (br s, 1H), 7.67 (br s, 1H), 7.43 (t, 1H), 6.85-6.81 (m, 2H), 4.57-4.20 (m, 4H), 3.94 (s, 3H), 3.47-3.40 (m, 1H), 2.10-2.00 (m, 2H), 1.33 (m, 10H), 0.86 (s, 9H), 0.07 (s, 6H); 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-70c83045ed484247b1f75e775cb6f000
Quelldatensatz
uspto-grants-2010_02
Patentnummer
US07659279B2

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