Diisopropylethylamine → HCID 44252463, 화합물

HRID 19113노트

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HRID 19113 반응식
[CH2:1]([O:3][C:4]1[C:5]([F:25])=[C:6]([CH:22]=[CH:23][CH:24]=1)[O:7][C:8]1[CH2:12][N:11]([C@@H:13]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:14]([OH:16])=O)[C:10](=[O:21])[CH:9]=1)[CH3:2].Cl.[OH:27][C@@H:28]([CH2:58]O)[CH2:29][N:30]1[CH:34]=[CH:33][C:32]([NH:35]C(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=[N:31]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=C[C:70]=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[OH:27][C:28]([CH3:58])([CH3:70])[CH2:29][N:30]1[CH:34]=[CH:33][C:32]([NH:35][C:14](=[O:16])[C@@H:13]([N:11]2[CH2:12][C:8]([O:7][C:6]3[CH:22]=[CH:23][CH:24]=[C:4]([O:3][CH2:1][CH3:2])[C:5]=3[F:25])=[CH:9][C:10]2=[O:21])[CH2:17][CH:18]([CH3:20])[CH3:19])=[N:31]1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 66893599HCID 66893599, 화합물HCID 66899094HMS5552 HCl

생성물 1

HCID 44252463HCID 44252463, 화합물수율 55%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

To a solution of (S)-2-[4-(3-ethoxy-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (0.460 g, 1.31 mmol) in N,N-dimethylformamide (10 mL) was added 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032, Example 80, 0.264 g, 1.70 mmol), and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (1.22 g, 2.76 mmol). The mixture was stirred at 0° C. and N,N-diisopropylethylamine (0.340 g, 2.63 mmol) was added. The mixture was stirred at room temperature for 7 h and the solvents were evaporated. The residue was treated with ethyl acetate and ammonium chloride solution, and the organic layer separated. The organic layer was washed with brine and dried over sodium sulfate. The solvents were evaporated and the residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 25 g, 30% to 100% ethyl acetate/hexanes) which afforded (S)-2-[4-(3-ethoxy-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (0.350 g, 55%) as a yellow solid: HR-ES-MS m/z calculated for C25H33FN4O5 [M+H]+ 489.2508, observed 489.2508, 1H NMR (300 MHz, DMSO-d6) δ ppm 1.00 0.90 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H), 1.05 (br. s., 3H), 1.06 (br. s., 3H), 1.36 (t, J=6.8 Hz, 3H), 1.47 (br. s., 1H), 1.50-1.64 (m, 1H), 1.63-1.86 (m, 1H), 3.89 (s, 2H), 4.15 (q, J=6.8 Hz, 2H), 4.21 (d, J=18.7 Hz, 1H), 4.60 (d, J=18.7 Hz, 1H), 4.68 (s, 1H), 4.83-4.93 (m, 1H), 4.89 (s, 1H), 6.44 (d, J=2.1 Hz, 1H), 6.96-7.07 (m, 1H), 7.07-7.26 (m, 2H), 7.53 (d, J=2.1 Hz, 1H), 10.80 (s, 1H).

후처리

  1. stirringThe mixture was stirred at room temperature for 7 h
  2. customthe solvents were evaporated
  3. additionThe residue was treated with ethyl acetate and ammonium chloride solution
  4. customthe organic layer separated
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvents were evaporated
  8. customthe residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 25 g, 30% to 100% ethyl acetate/hexanes) which

출처 및 근거

ORD 기록
ord-6f754f91f2ac44e09def8b86ec710538
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741327B2

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