Diisopropylethylamine → 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-4-trifluoromethyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide

HRID 19316Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 19316
[Cl:1][C:2]1[CH:28]=[CH:27][CH:26]=[CH:25][C:3]=1[O:4][C:5]1[CH2:9][N:8]([CH:10]([CH2:14][CH:15]([C:20]([F:23])([F:22])[F:21])[C:16]([F:19])([F:18])[F:17])[C:11](O)=[O:12])[C:7](=[O:24])[CH:6]=1.[CH3:29][C:30]1([CH3:42])[O:34][C@H:33]([CH2:35][N:36]2[CH:40]=[CH:39][C:38]([NH2:41])=[N:37]2)[CH2:32][O:31]1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C>[CH3:29][C:30]1([CH3:42])[O:34][C@H:33]([CH2:35][N:36]2[CH:40]=[CH:39][C:38]([NH:41][C:11](=[O:12])[CH:10]([N:8]3[CH2:9][C:5]([O:4][C:3]4[CH:25]=[CH:26][CH:27]=[CH:28][C:2]=4[Cl:1])=[CH:6][C:7]3=[O:24])[CH2:14][CH:15]([C:20]([F:22])([F:23])[F:21])[C:16]([F:19])([F:17])[F:18])=[N:37]2)[CH2:32][O:31]1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amineHCID 866352392-[4-(2-Chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-4-trifluoromethyl-pentanoic acid

Produkt 1

HCID 866352402-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-4-trifluoromethyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amideAusbeute 77,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

In a round bottom flask under argon was placed 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-4-trifluoromethyl-pentanoic acid (31 mg, 0.072 mmol) and 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 20 mg, 0.086 mmol) in N,N-dimethylformamide (1 mL). To this mixture was added N,N-diisopropyethylamine (35 μL, 0.22 mmol) and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (48 mg, 0.11 mmol) and stirred overnight at 25° C. After this time, the mixture was diluted with ethyl acetate (15 mL) and washed with a saturated aqueous solution of ammonium chloride (10 mL), saturated aqueous solution of sodium bicarbonate (10 mL) and a saturated aqueous solution of sodium chloride (10 mL), dried over sodium sulfate, and concentrated with silica gel (1.5 g). Purification by Biotage flash chromatography (AnaLogix 12 g column, 40% ethyl acetate/hexanes) afforded 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-4-trifluoromethyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (34 mg, 77%) as a cream colored foam: HR-ES-MS m/z calculated for C25H25N4O5ClF6 [M+H]+ 611.1491, observed 611.1487.

Aufarbeitung

  1. customIn a round bottom flask under argon was placed
  2. washwashed with a saturated aqueous solution of ammonium chloride (10 mL), saturated aqueous solution of sodium bicarbonate (10 mL)
  3. dry with materiala saturated aqueous solution of sodium chloride (10 mL), dried over sodium sulfate
  4. concentrationconcentrated with silica gel (1.5 g)
  5. customPurification by Biotage flash chromatography (AnaLogix 12 g column, 40% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-c350970964dd4733830afcb7ffc0465d
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741327B2

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