tert-Butanol → Tert-butyl 3-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzoate

HRID 2093031Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2093031
C(O)(C)(C)C.CCN(C(C)C)C(C)C.Cl[C:16]1[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]2[CH:28]=[C:29]([CH:37]=[CH:38][CH:39]=2)[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[N:17]=1.C(O)(=O)C.[NH2:44][CH2:45][C:46]1[C:47]([N:52]([CH3:57])[S:53]([CH3:56])(=[O:55])=[O:54])=[N:48][CH:49]=[CH:50][CH:51]=1>ClCCCl>[CH3:57][N:52]([S:53]([CH3:56])(=[O:55])=[O:54])[C:47]1[C:46]([CH2:45][NH:44][C:16]2[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]3[CH:28]=[C:29]([CH:37]=[CH:38][CH:39]=3)[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[N:17]=2)=[CH:51][CH:50]=[CH:49][N:48]=1

Komponenten

6

Edukt 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 57584682Tert-butyl 3-({4-chloro-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzoateHCID 67099950N-(3-(Aminomethyl)pyridin-2-yl)-N-methylmethanesulfonamide acetate

Produkt 1

HCID 25116907Tert-butyl 3-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzoate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 111,2-DichloroethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A solution of tert-butanol (20.0 mL), DCE (20.0 mL) and DIEA (3.13 mL, 18.0 mmol) was treated with C8 (5.60 g, 15.0 mmol) and B5 (5.02 g, 15.0 mmol), and the resulting mixture was stirred at 80° C. under an atmosphere of nitrogen for 16 hours. The mixture was cooled to 25° C. and concentrated. The resultant residue was partitioned between EtOAc and 1 N sodium hydroxide, and the organic phase was collected. The aqueous layer was extracted with EtOAc, and the combined organic phases were dried over MgSO4 and filtered. The resultant filtrate was concentrated under reduced pressure, and the resultant residue was triturated with hot EtOAc to provide 9 as a white solid. Yield: 7.83 grams, 95%. LC/MS (standard) 25°=3.0 min., m/z 553.6 (MH+). HPLC (FAK1) 25°=8.14 min. 1H NMR (d6-DMSO) δ: 9.75 (bs, 1H), 8.44 (d, J=5.2 Hz., 1H), 8.29 (s, 1H), 8.05 (bs, 1H), 7.82 (d, J=7.8 Hz., 1H), 7.60 (t, J=5.7 Hz., 1H), 7.44-7.40 (m, 2H), 7.17 (t, J=5.7 Hz, 1H), 4.82 (d, J=5.7 Hz., 2 H), 3.16 (s, 3H), 3.13 (s, 3H), 1.51 (s, 9H) ppm. FAK IC50: 0.0006 μM

Aufarbeitung

  1. temperatureThe mixture was cooled to 25° C.
  2. concentrationconcentrated
  3. customThe resultant residue was partitioned between EtOAc and 1 N sodium hydroxide
  4. customthe organic phase was collected
  5. extractionThe aqueous layer was extracted with EtOAc
  6. dry with materialthe combined organic phases were dried over MgSO4
  7. filtrationfiltered
  8. concentrationThe resultant filtrate was concentrated under reduced pressure
  9. customthe resultant residue was triturated with hot EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-2dd935c1411c4812a902bcb1a348d05b
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08440822B2

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