Methanol → Trifluoroacetic acid

HRID 2246573ノート

反応式

HRID 2246573 の反応式
[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]

参加物

7

反応物 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

生成物 2

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

試薬・触媒・溶媒 1

HCID 23938Palladium触媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-d5fae43c797e48debaeb7d48f3db73d1
出典データセット
uspto-grants-2010_03
特許番号
US07687508B2

反応ノート

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