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Tributylphosphine → 4-(4-Chloro-2-fluorophenoxy)-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline

HRID 495383
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Reaktionsgleichung von HRID 495383
[O:1]=[S:2]1(=[O:12])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Cl:31][C:32]1[CH:51]=[CH:50][C:35]([O:36][C:37]2[C:46]3[C:41](=[CH:42][C:43](O)=[C:44]([O:47][CH3:48])[CH:45]=3)[N:40]=[CH:39][N:38]=2)=[C:34]([F:52])[CH:33]=1.C(P(CCCC)CCCC)CCC>C(OCC)C.C(Cl)Cl>[Cl:31][C:32]1[CH:51]=[CH:50][C:35]([O:36][C:37]2[C:46]3[C:41](=[CH:42][C:43]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][S:2](=[O:1])(=[O:12])[CH2:3][CH2:4]4)=[C:44]([O:47][CH3:48])[CH:45]=3)[N:40]=[CH:39][N:38]=2)=[C:34]([F:52])[CH:33]=1
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Komponenten

7

Edukt 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 114354734-(3-Hydroxypropyl)thiomorpholine 1,1-DioxideHCID 1356162044-(4-Chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline

Produkt 1

HCID 219359994-(4-Chloro-2-fluorophenoxy)-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazolineAusbeute 69,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propan-1-ol (4.2 g) and 1,1′-(azodicarbonyl)dipiperidine (11.7 g) were added in turn to a mixture of 4(4-chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (5.0 g), tributylphosphine (11.1 ml) and methylene chloride (150 ml). The resultant mixture was stirred at ambient temperature overnight. The mixture was diluted with diethyl ether (300 ml) and the precipitate was removed by filtration. The filtrate was evaporated and the residue was purified by column chromatography on silica using a 19:1 mixture of methylene chloride and methanol as eluent. The material so obtained was triturated under ethyl acetate and dried to give 4-(4-chloro-2fluorophenoxy)-7-[3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy]-6-methoxyquinazoline (5.4 g); NMR Spectrum: (DMSOd6) 1.86 (m, 2H), 2.65 (t, 2H), 2.92 (m, 4H), 3.08 (m, 4H), 3.97 (s, 3H), 4.26 (t, 2H), 7.4 (m, 1H), 7.42 (s, 1H), 7.56 (m, 2H), 7.68 (m, 1H), 8.54 (s, 1H).

Aufarbeitung

  1. customthe precipitate was removed by filtration
  2. customThe filtrate was evaporated
  3. customthe residue was purified by column chromatography on silica using
  4. additiona 19:1 mixture of methylene chloride and methanol as eluent
  5. customThe material so obtained
  6. customwas triturated under ethyl acetate
  7. customdried

Quellen und Nachweise

ORD-Eintrag
ord-0c875ae2e1e6419ebfc4968147179c3b
Quelldatensatz
uspto-grants-2005_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US06939866B2

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