Triphenylphosphine → N-{3-[3-(4-benzyloxybutyl)-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

HRID 75679

Reaktionsgleichung

Reaktionsgleichung von HRID 75679
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:11]([CH3:34])[C:12](=[O:33])[C:13]([CH3:32])=[C:14]2[C:19]=1[C:18](=[O:20])[NH:17][C:16](=[O:21])[N:15]2[C:22]1[CH:23]=[C:24]([NH:28][C:29](=[O:31])[CH3:30])[CH:25]=[CH:26][CH:27]=1.[CH2:35]([O:42][CH2:43][CH2:44][CH2:45][CH2:46]O)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1.C(OCC)(=O)C.O>[CH2:35]([O:42][CH2:43][CH2:44][CH2:45][CH2:46][N:17]1[C:18](=[O:20])[C:19]2=[C:10]([NH:9][C:3]3[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=3[F:1])[N:11]([CH3:34])[C:12](=[O:33])[C:13]([CH3:32])=[C:14]2[N:15]([C:22]2[CH:23]=[C:24]([NH:28][C:29](=[O:31])[CH3:30])[CH:25]=[CH:26][CH:27]=2)[C:16]1=[O:21])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Komponenten

8

Edukt 4

HCID 11776Triphenylphosphine2×HCID 75555Diisopropyl diazene-1,2-dicarboxylate2×HCID 5622124-Benzyloxy-1-butanol2×HCID 59717419N-{3-[5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

Produkt 1

HCID 59717314N-{3-[3-(4-benzyloxybutyl)-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamideAusbeute 77 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Under argon atmosphere, to a suspension of N-{3-[5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 89 (75.0 mg), 4-benzyloxybutyl alcohol 90 (25.0 μl) and triphenylphosphine (37.0 mg) in tetrahydrofuran (1.00 ml) was added diisopropyl azodicarboxylate (28.0 μl) with stirring under ice cooling. The mixture was stirred at the same temperature for 2 hrs, and 4-benzyloxybutyl alcohol (13.0 μl), triphenylphosphine (19.0 mg) and diisopropyl azodicarboxylate (14.0 μl) were added. The mixture was stirred at the same temperature for 1 hr, and water and ethyl acetate were added to allow partitioning. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (chloroform:ethyl acetate=2:1→1:1) and thin layer chromatography (hexane:acetone=1:1) for further purification to give N-{3-[3-(4-benzyloxybutyl)-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 91 (74 mg, yield 77%) as a pale-yellow amorphous form.

Aufarbeitung

  1. stirringThe mixture was stirred at the same temperature for 2 hrs
  2. stirringThe mixture was stirred at the same temperature for 1 hr
  3. customto allow partitioning
  4. washThe organic layer was washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (chloroform:ethyl acetate=2:1→1:1) and thin layer chromatography (hexane:acetone=1:1) for further purification

Quellen und Nachweise

ORD-Eintrag
ord-1106c38fde70447aabef97bdc5801f08
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08835443B2

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