Triethylamine → ethyl (E)-7-[2-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenyl]-vinyl]-1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylate

HRID 963434

Reaktionsgleichung

Reaktionsgleichung von HRID 963434
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:15]=[C:16](I)[C:17]=1[O:18][CH3:19])[CH2:6][C:7]1[C:8]([NH2:14])=[N:9][C:10]([NH2:13])=[N:11][CH:12]=1.[CH:21]1([N:24]2[C:33]3[C:28](=[CH:29][C:30]([F:37])=[C:31]([CH:35]=[CH2:36])[C:32]=3[F:34])[C:27](=[O:38])[C:26]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:25]2)[CH2:23][CH2:22]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[NH2:13][C:10]1[N:9]=[C:8]([NH2:14])[C:7]([CH2:6][C:5]2[CH:4]=[C:3]([O:2][CH3:1])[C:17]([O:18][CH3:19])=[C:16](/[CH:36]=[CH:35]/[C:31]3[C:32]([F:34])=[C:33]4[C:28]([C:27](=[O:38])[C:26]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:25][N:24]4[CH:21]4[CH2:23][CH2:22]4)=[CH:29][C:30]=3[F:37])[CH:15]=2)=[CH:12][N:11]=1

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 111010945-(3,4-Dimethoxy-5-iodo-benzyl)pyrimidine-2,4-diamineHCID 15636884Ethyl 1-cyclopropyl-6,8-difluoro-7-vinyl-4-oxo-1,4-dihydro-quinoline-3-carboxylate

Produkt 1

HCID 86752726ethyl (E)-7-[2-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenyl]-vinyl]-1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylateAusbeute 49 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of 193 mg of 5-(3,4-dimethoxy-5-iodo-benzyl)-pyrimidine-2,4-diamine, 224 mg of ethyl 1-cyclopropyl-6,8-difluoro-7-vinyl-4-oxo-1,4-dihydro-quinoline-3-carboxylate (J. Heterocyclic Chem., 28, 1581 (1991)), 26 mg of triphenylphosphine, 0.084 ml of triethylamine and 11.2 mg of palladium acetate in 2 ml of dimethylformamide is heated at 100° for 5 hrs. The reaction mixture is cooled to room temperature, poured into 50 ml of water and extracted twice with 25 ml of ethyl acetate each time. The organic phases are washed twice with 25 ml of 2N aqueous hydrochloric acid each time. The hydrochloric acid phases are made basic with sodium bicarbonate and extracted three times with 25 ml of methylene chloride each time. The combined organic phases are washed with 25 ml of water, dried over magnesium sulphate and concentrated. The crude product is recrystallized from methylene chloride/diethyl ether. 140 mg (49%) of ethyl (E)-7-[2-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenyl]-vinyl]-1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylate are obtained as a yellowish solid. Mass spectrum (ISP): 578 (M++H, 100%).

Aufarbeitung

  1. temperatureis heated at 100° for 5 hrs
  2. extractionextracted twice with 25 ml of ethyl acetate each time
  3. washThe organic phases are washed twice with 25 ml of 2N aqueous hydrochloric acid each time
  4. extractionextracted three times with 25 ml of methylene chloride each time
  5. washThe combined organic phases are washed with 25 ml of water
  6. dry with materialdried over magnesium sulphate
  7. concentrationconcentrated
  8. customThe crude product is recrystallized from methylene chloride/diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-66fbcdabaca74c33a36ae53c009e6c5b
Quelldatensatz
uspto-grants-1998_06
Patentnummer
US05763450

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