Methanol → US8933228, Ref 2

HRID 239032Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 239032
C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.[C:13]([C:17]1[CH:21]=[C:20]([NH2:22])[N:19]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=2)[N:18]=1)([CH3:16])([CH3:15])[CH3:14].[NH2:30][C:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:34]([O:41][C:42]2[CH:47]=[CH:46][N:45]=[C:44]([NH:48][C:49](=[O:53])[CH2:50][O:51][CH3:52])[CH:43]=2)=[CH:33][CH:32]=1.CO>C(Cl)Cl>[C:13]([C:17]1[CH:21]=[C:20]([NH:22][C:6](=[O:7])[NH:30][C:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[C:34]([O:41][C:42]3[CH:47]=[CH:46][N:45]=[C:44]([NH:48][C:49](=[O:53])[CH2:50][O:51][CH3:52])[CH:43]=3)=[CH:33][CH:32]=2)[N:19]([C:23]2[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=2)[N:18]=1)([CH3:16])([CH3:15])[CH3:14]

Komponenten

6

Edukt 4

HCID 887MethanolHCID 682631,1'-CarbonyldiimidazoleHCID 29741323-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-amineHCID 66718180N-(4-(4-Aminonaphthalen-1-yloxy)pyridin-2-yl)-2-methoxyacetamide

Produkt 1

HCID 46218331US8933228, Ref 2Ausbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a stirred suspension of CDI (28.8 g, 178 mmol) in DCM (250 mL) at RT, under nitrogen, was added 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-amine (7) (40.7 g, 178 mmol) portion-wise over 1 hr. After 1 hr the resulting dark red solution was added dropwise, over 1 hr, to a stirred solution of N-(4-(4-aminonaphthalen-1-yloxy)pyridin-2-yl)-2-methoxyacetamide (12) (35.5 g, 99 mmol) in DCM (1 L). After 1 hr MeOH (100 mL) was added and the mixture was kept at RT for 16 hr. The reaction mixture was evaporated in vacuo and the residue was taken up into DCM (500 mL) and was washed with water and saturated aqueous NaHCO3 solution (500 mL). The organic layer was dried (MgSO4), evaporated in vacuo and the residue purified by flash column chromatography (SiO2, 800 g, 2% MeOH in DCM, isocratic elution). This product was recrystallized from ethyl acetate/heptane (800 mL of a 5:3 v/v mixture) to afford N-(4-(4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)pyridin-2-yl)-2-methoxyacetamide (1) (25.5 g, 45%) as a white powder. Found: C, 68.41; H, 5.93; N, 14.36; C33H34N6O4 requires: C, 68.49; H, 5.92; N, 14.52%.

Aufarbeitung

  1. customThe reaction mixture was evaporated in vacuo
  2. washwas washed with water and saturated aqueous NaHCO3 solution (500 mL)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. customevaporated in vacuo
  5. customthe residue purified by flash column chromatography (SiO2, 800 g, 2% MeOH in DCM, isocratic elution)
  6. customThis product was recrystallized from ethyl acetate/heptane (800 mL of a 5:3 v/v mixture)

Quellen und Nachweise

ORD-Eintrag
ord-883d0d8fa3634a569fa13559a3983d44
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642773B2

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