Diisopropylethylamine → N-(2-acetamidopyrimidin-5-yl)-6-chloro-3-(3-(trifluoromethyl)phenylamino)benzo[d]isoxazole-7-carboxamide

HRID 253700Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 253700
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]2[C:6]([NH:9][C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=3)=[N:7][O:8][C:4]=2[C:3]=1[C:22]([OH:24])=O.CCN(C(C)C)C(C)C.[NH2:34][C:35]1[CH:36]=[N:37][C:38]([NH:41][C:42](=[O:44])[CH3:43])=[N:39][CH:40]=1>CN(C=O)C>[C:42]([NH:41][C:38]1[N:39]=[CH:40][C:35]([NH:34][C:22]([C:3]2[C:4]3[O:8][N:7]=[C:6]([NH:9][C:10]4[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:17])([F:19])[F:18])[CH:11]=4)[C:5]=3[CH:20]=[CH:21][C:2]=2[Cl:1])=[O:24])=[CH:36][N:37]=1)(=[O:44])[CH3:43]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 20387481N-(5-aminopyrimidin-2-yl)acetamideHCID 441404356-Chloro-3-(3-(trifluoromethyl)phenylamino)benzo[d]isoxazole-7-carboxylic acid

Produkt 1

HCID 25068624N-(2-acetamidopyrimidin-5-yl)-6-chloro-3-(3-(trifluoromethyl)phenylamino)benzo[d]isoxazole-7-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A round-bottomed flask was charged with 6-chloro-3-(3-(trifluoromethyl)phenylamino)benzo[d]isoxazole-7-carboxylic acid (0.1 g, 0.28 mmol, made by the method described in Example 1), n,n-diisopropylethylamine (0.07 mL, 0.42 mmol), o-(7-azabenzotriazol-1-yl)-n,n,n′,n-tetramethyluronium hexafluorophosphate (0.15 g, 0.39 mmol), and DMF (1 mL). This mixture was stirred for 15 min before N-(5-aminopyrimidin-2-yl)acetamide (0.045 g, 0.29 mmol, Step B) was introduced. The reaction mixture was stirred at 60° C. for 16 h, then partitioned between EtOAc (15 ml) and brine (10 mL). The aqueous layer was back exacted with EtOAc (3×10 mL) and the combined EtOAc layer was dried (Na2SO4) and concentrated. The crude product was dissolved in DCM and chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 0% to 4% of MeOH in CH2Cl2, to provide N-(2-acetamidopyrimidin-5-yl)-6-chloro-3-(3-(trifluoromethyl)phenylamino)benzo[d]isoxazole-7-carboxamide as an off-white solid. MS (ESI, pos. ion) m/z: 491 (M+1).

Aufarbeitung

  1. additionwas introduced
  2. custompartitioned between EtOAc (15 ml) and brine (10 mL)
  3. dry with materialthe combined EtOAc layer was dried (Na2SO4)
  4. concentrationconcentrated
  5. dissolutionThe crude product was dissolved in DCM
  6. customchromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
  7. washeluting with a gradient of 0% to 4% of MeOH in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-16e893917d754908970c2836eb90c14b
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07872128B2

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