Methanol → Trifluoroacetic acid

HRID 2246573노트

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HRID 2246573 반응식
[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]

참가 물질

7

반응물 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

생성물 2

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

시약·촉매·용매 1

HCID 23938Palladium촉매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-d5fae43c797e48debaeb7d48f3db73d1
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07687508B2

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