1,1'-Carbonyldiimidazole → N-[4-(4-Bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carbonyl]-C-phenyl-methanesulfonamide

HRID 1366069Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1366069
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:18]([OH:20])=O)=[CH:11][N:12]([CH3:17])[C:13](=[O:16])[C:14]=2[CH3:15])=[C:4]([F:21])[CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:34]1([CH2:40][S:41]([NH2:44])(=[O:43])=[O:42])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C1CCN2C(=NCCC2)CC1>CN(C=O)C.CCOC(C)=O.Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:18]([NH:44][S:41]([CH2:40][C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)(=[O:42])=[O:43])=[O:20])=[CH:11][N:12]([CH3:17])[C:13](=[O:16])[C:14]=2[CH3:15])=[C:4]([F:21])[CH:3]=1

Komponenten

8

Edukt 4

HCID 682631,1'-CarbonyldiimidazoleHCID 78318BenzenemethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 116460904-(4-Bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid2×

Produkt 1

HCID 57636909N-[4-(4-Bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carbonyl]-C-phenyl-methanesulfonamideAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 313Hydrochloric AcidLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

N-[4-(4-Bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carbonyl]-C-phenyl-methanesulfonamide was prepared from 4-(4-bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid as follows. To a solution of 4-(4-bromo-2-fluorophenylamino) 1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (0.040 mg, 0.113 mmol) in DMF (1.5 mL) was added 1,1′-carbonyldiimidazole (0.074 mg, 0.456 mmol). After stirring for two hours, α-toluenesulfonamide (0.079 mg, 0.461 mmol) was added, followed by DBU (0.070 mL, 0.459 mmol). After stirring for 16 hours at room temperature, the reaction mixture was diluted with EtOAc and 1N HCl solution. The organic layer was separated and washed with brine. The aqueous layer was extracted with EtOAc (2×) and washed with brine. The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure. Purification by flash column chromatography (2% MeOH in methylene chloride) gave 0.039 g (68%) clean desired product; MS APCI (−) m/z 506, 508 (M−, Br pattern) detected; 1H NMR (400 MHz, CD3OD) δ 8.29 (s, 1H), 7.27 (m, 3H), 7.18 (d, 1H), 7.11 (m, 3H), 6.56 (t, 1H), 4.44 (s, 2H), 3.54 (s, 3H), 1.62 (s, 3H).

Aufarbeitung

  1. stirringAfter stirring for 16 hours at room temperature
  2. customThe organic layer was separated
  3. washwashed with brine
  4. extractionThe aqueous layer was extracted with EtOAc (2×)
  5. washwashed with brine
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash column chromatography (2% MeOH in methylene chloride)

Quellen und Nachweise

ORD-Eintrag
ord-91ec4550833c434ebfc2033226bbea59
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07893065B2

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