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Nitrogen → 2-(1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-[2-(3-fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-cyclopentanecarboxylic acid tert-butyl ester

HRID 1443502
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C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:20]([O:24][C:25]([C@@H:27]1[CH2:31][C@@H:30]([OH:32])[CH2:29][C@H:28]1[C:33](=[O:45])[NH:34][C@:35]1([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:37][C@H:36]1[CH:38]=[CH2:39])=[O:26])([CH3:23])([CH3:22])[CH3:21].[F:46][C:47]1[CH:48]=[C:49]([C:53]2[N:62]=[C:61](O)[C:60]3[C:55](=[C:56]([CH3:66])[C:57]([O:64][CH3:65])=[CH:58][CH:59]=3)[N:54]=2)[CH:50]=[CH:51][CH:52]=1.N#N.CC(OC(/N=N/C(OC(C)C)=O)=O)C>CN(C=O)C.C1COCC1>[C:20]([O:24][C:25]([CH:27]1[CH2:31][CH:30]([O:32][C:61]2[C:60]3[C:55](=[C:56]([CH3:66])[C:57]([O:64][CH3:65])=[CH:58][CH:59]=3)[N:54]=[C:53]([C:49]3[CH:50]=[CH:51][CH:52]=[C:47]([F:46])[CH:48]=3)[N:62]=2)[CH2:29][CH:28]1[C:33](=[O:45])[NH:34][C:35]1([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:37][CH:36]1[CH:38]=[CH2:39])=[O:26])([CH3:23])([CH3:21])[CH3:22]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 5

HCID 947NitrogenHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 59165438(1R,2R,4S)-2-((1R,2S)-1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl) 4-hydroxy-cyclopentanecarboxylic acid tert-butyl esterHCID 1784877302-(3-fluorophenyl)-7-methoxy-8-methyl-1H-quinazolin-4-one

Produkt 1

HCID 68412461
2-(1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-[2-(3-fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-cyclopentanecarboxylic acid tert-butyl ester
Ausbeute 94,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

PPh3 (787 mg, 3.0 mmol) was added to a stirred solution of the alcohol 15 (550 mg, 1.5 mmol) and the quinazolinol 127 (430 mg, 1.5 mmol) in a mixture of dry THF (40 mL) and dry DMF 10 mL. The reaction mixture was put under inert atmosphere (N2) at room temperature and DIAD (591 μL, 3.0 mmol) was added. The reaction mixture was stirred for 18 h whereafter the solvents were evaporated. The residue was dissolved in CHCl3 and washed with brine in a separatory funnel. The organic phase was dried with Na2SO4, evaporated on silica and purified by flash chromatography (heptane:ethyl acetate 2:1 to 1:1) which gave the title compound as a white-beige solid (896 mg, 94%), LRMS (M+H) 634.

Aufarbeitung

  1. customwere evaporated
  2. dissolutionThe residue was dissolved in CHCl3
  3. washwashed with brine in a separatory funnel
  4. dry with materialThe organic phase was dried with Na2SO4
  5. customevaporated on silica
  6. custompurified by flash chromatography (heptane:ethyl acetate 2:1 to 1:1) which

Quellen und Nachweise

ORD-Eintrag
ord-e5e4964dc36f4ca39e569d7dd1bf4318
Quelldatensatz
uspto-grants-2010_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07659245B2

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