Methanol → Trifluoroacetic acid

HRID 2246573Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2246573
[C:1]([NH:4][C@@H:5]1[CH2:10][C@H:9]([N:11]([CH:13]([CH3:15])[CH3:14])C)[CH2:8][CH2:7][C@@H:6]1[N:16]1[CH2:20][CH2:19][C@H:18]([NH:21][C:22](=O)OCC2C=CC=CC=2)[C:17]1=[O:32])(=[O:3])[CH3:2].ClC1[C:43]2[C:38](=[CH:39][CH:40]=[C:41]([C:44]([F:47])([F:46])[F:45])[CH:42]=2)[N:37]=[CH:36][N:35]=1.C(N(C(C)C)CC)(C)C.[CH3:57][OH:58]>[Pd]>[CH:13]([NH:11][C@H:9]1[CH2:10][C@@H:5]([NH:4][C:1](=[O:3])[CH3:2])[C@@H:6]([N:16]2[CH2:20][CH2:19][C@H:18]([NH:21][C:22]3[C:39]4[C:38](=[CH:43][CH:42]=[C:41]([C:44]([F:45])([F:46])[F:47])[CH:40]=4)[N:37]=[CH:36][N:35]=3)[C:17]2=[O:32])[CH2:7][CH2:8]1)([CH3:14])[CH3:15].[C:57]([OH:3])([C:44]([F:47])([F:46])[F:45])=[O:58]

Komponenten

7

Edukt 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 210750954-Chloro-6-(trifluoromethyl)quinazolineHCID 44185160benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

Produkt 2

HCID 6422Trifluoroacetic acidAusbeute 93 %HCID 24794624N-((1R,2S,5R)-5-(isopropylamino)-2-((3S)-2-oxo-3-((6-(trifluoromethyl)-4-quinazolinyl)amino)-1-pyrrolidinyl)cyclohexyl)acetamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 23938PalladiumKatalysator

Versuchsvorschrift

To a solution of benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-(isopropylamino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (30 mg, 0.07 mmol; see Example 1, Step 8) in methanol (3 mL) was added 10% Pd/C (30 mg of 50% wet catalyst). The flask was evacuated and back-filled with hydrogen from a hydrogen balloon. The mixture was stirred at room temperature for 1.5 h under 1 atm hydrogen and then the catalyst was removed by filtration. The filtrate was concentrated in vacuo. The residue was dissolved in isopropanol (3 mL) and charged sequentially with 4-chloro-6-(trifluoromethyl)quinazoline (19.4 mg, 1.2 eq) and diisopropylethylamine (18 mg, 2 eq). The mixture was stirred at room temperature for 1 h. The solvent was removed under reduced pressure. The residue was purified by preparative reverse-phase HPLC to provide the title compound as its TFA salt (47 mg, 93%). LC/MS found [M+H]+=493. 1H-NMR (400 MHz, CD3OD), δ ppm: 8.90 (1H, s), 8.81 (1H, s), 8.25-8.29 (1H, m), 7.96 (1H, d, J=8.65 Hz), 5.44 (1H, t, J=9.92 Hz), 4.42 (1H, d, J=2.54 Hz), 4.15-4.24 (1H, m), 3.90 (1H, t, J=8.65 Hz), 3.70-3.79 (1H, m), 3.46-3.62 (2H, m), 2.56-2.67 (1H, m), 2.33-2.47 (1H, m), 1.70-2.23 (9H, m), 1.35 (6H, d, J=6.10 Hz).

Aufarbeitung

  1. customThe flask was evacuated
  2. additionback-filled with hydrogen from a hydrogen balloon
  3. customthe catalyst was removed by filtration
  4. concentrationThe filtrate was concentrated in vacuo
  5. dissolutionThe residue was dissolved in isopropanol (3 mL)
  6. stirringThe mixture was stirred at room temperature for 1 h
  7. customThe solvent was removed under reduced pressure
  8. customThe residue was purified by preparative reverse-phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-d5fae43c797e48debaeb7d48f3db73d1
Quelldatensatz
uspto-grants-2010_03
Patentnummer
US07687508B2

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