Diisopropylethylamine → N-(4-(4-(3-(3-(tert-Butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)ureido)-1-naphthoyl)pyridin-2-yl)-2-(2-methoxyethoxy)acetamide

HRID 571116

Reaktionsgleichung

Reaktionsgleichung von HRID 571116
[NH2:1][C:2]1[CH:3]=[C:4]([CH:37]=[CH:38][N:39]=1)[C:5]([C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([NH:17][C:18]([NH:20][C:21]2[N:25]([C:26]3[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=3)[N:24]=[C:23]([C:33]([CH3:36])([CH3:35])[CH3:34])[CH:22]=2)=[O:19])=[CH:9][CH:8]=1)=[O:6].CCN(C(C)C)C(C)C.[CH3:49][O:50][CH2:51][CH2:52][O:53][CH2:54][C:55](Cl)=[O:56]>C1COCC1>[C:33]([C:23]1[CH:22]=[C:21]([NH:20][C:18](=[O:19])[NH:17][C:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:7]([C:5]([C:4]3[CH:37]=[CH:38][N:39]=[C:2]([NH:1][C:55](=[O:56])[CH2:54][O:53][CH2:52][CH2:51][O:50][CH3:49])[CH:3]=3)=[O:6])=[CH:8][CH:9]=2)[N:25]([C:26]2[CH:27]=[CH:28][C:29]([CH3:32])=[CH:30][CH:31]=2)[N:24]=1)([CH3:34])([CH3:35])[CH3:36]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 70103382-(2-Methoxyethoxy)acetyl chlorideHCID 674592551-(4-(2-aminoisonicotinoyl)naphthalen-1-yl)-3-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)urea

Produkt 1

HCID 54589301N-(4-(4-(3-(3-(tert-Butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)ureido)-1-naphthoyl)pyridin-2-yl)-2-(2-methoxyethoxy)acetamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 1-(4-(2-aminoisonicotinoyl)naphthalen-1-yl)-3-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)urea (38.0 mg, 0.073 mmol) and DIPEA (64 μL, 0.37 mmol) in dry THF (4.0 mL) under N2 at 0° C. was added 2-(2-methoxyethoxy)acetyl chloride (45.0 mg, 0.29 mmol). The reaction mixture was maintained at 0° C. for 30 min and was then warmed to RT for 1.5 hr. The reaction was quenched by the addition of a solution of NH3 (1% in MeOH, 3.0 mL) and after a further 45 min at RT was evaporated in vacuo. The residue was purified by SCX capture and release followed by flash column chromatography (SiO2, 12 g, [5% MeOH in EtOAc] in isohexane, 0-60%, gradient elution) to afford the title compound, Example 22, as a yellow solid (21 mg, 44%); Rt 2.67 min (Method 2); m/z 635 (M+H)+ (ES+); 1H NMR (400 MHz, DMSO-d6) δ: 1.29 (9H, s), 2.39 (3H, s), 3.29 (3H, s), 3.50 (2H, m), 3.66 (2H, m), 4.14 (2H, s), 6.45 (1H, s), 7.35-7.37 (3H, overlapping m), 7.46 (2H, d), 7.67-7.73 (3H, overlapping m), 8.20 (2H, m), 8.37 (1H, s), 8.49 (1H, m), 8.54 (1H, d), 9.03 (1H, s), 9.47 (1H, s), 10.24 (1H, s).

Aufarbeitung

  1. temperaturewas then warmed to RT for 1.5 hr
  2. customThe reaction was quenched by the addition of a solution of NH3 (1% in MeOH, 3.0 mL) and after a further 45 min at RT
  3. customwas evaporated in vacuo
  4. customThe residue was purified by SCX capture and release
  5. washfollowed by flash column chromatography (SiO2, 12 g, [5% MeOH in EtOAc] in isohexane, 0-60%, gradient elution)

Quellen und Nachweise

ORD-Eintrag
ord-30cf090e4d8449c892f57bcab8f4da71
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09024041B2

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