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Diisopropylethylamine → (S)-2-{4-[3-(2-hydroxy-2-methyl-propyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide

HRID 19376
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HRID 19376 반응식
[OH:1][C:2]([CH3:26])([CH3:25])[CH2:3][C:4]1[CH:5]=[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.Cl.[OH:28][C@@H:29]([CH2:59]O)[CH2:30][N:31]1[CH:35]=[CH:34][C:33]([NH:36]C(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=[N:32]1.[CH:61](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>[OH:28][C:29]([CH3:59])([CH3:61])[CH2:30][N:31]1[CH:35]=[CH:34][C:33]([NH:36][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]([CH2:3][C:2]([OH:1])([CH3:26])[CH3:25])[CH:5]=3)=[CH:9][C:10]2=[O:21])[CH2:17][CH:18]([CH3:20])[CH3:19])=[N:32]1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 66895240HCID 66895240, 화합물HCID 66899094HMS5552 HCl

생성물 1

HCID 57920169(S)-2-{4-[3-(2-hydroxy-2-methyl-propyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide
수율 30%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of (S)-2-{4-[3-(2-hydroxy-2-methyl-propyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid (prepared as in Example 235, 0.159 g, 0.44 mmol) in N,N-dimethylformamide (5 mL) was added 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 0.102 g, 0.66 mmol), N,N-diisopropylethylamine (0.312 g, 2.41 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.778 g, 1.76 mmol) at 0° C. The mixture was allowed to slowly warm up to room temperature and stirred for 48 h. The mixture was then concentrated in vacuo, the residue taken up in ethyl acetate and washed with aqueous saturated ammonium chloride and brine and then dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by ISCO column chromatography (Silicycle 40 g, 10% to 100% ethyl acetate/hexanes) which afforded (S)-2-{4-[3-(2-hydroxy-2-methyl-propyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (0.060 g, 30%) as a white solid: HR-ES-MS m/z calculated for C27H38N4O5 [M+H]+ 499.2915, observed 499.2915; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.83-0.97 (m, 6H), 1.06 (br. s., 12H), 1.36-1.63 (m, 2H), 1.66-1.86 (m, 1H), 2.68 (s, 2H), 3.89 (s, 2H), 4.18 (d, J=18.1 Hz, 1H), 4.37 (d, J=1.8 Hz, 1H), 4.57 (d, J=18.1 Hz, 1H), 4.68 (d, J=1.5 Hz, 1H), 4.83 (s, 1H), 4.84-4.94 (m, 1H), 6.44 (s, 1H), 7.07-7.19 (m, 3H), 7.27-7.42 (m, 1H), 7.54 (s, 1H), 10.78 (s, 1H).

후처리

  1. concentrationThe mixture was then concentrated in vacuo
  2. washwashed with aqueous saturated ammonium chloride and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by ISCO column chromatography (Silicycle 40 g, 10% to 100% ethyl acetate/hexanes) which

출처 및 근거

ORD 기록
ord-ffd37df479c14c65923be94202df6ca8
출처 데이터셋
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07741327B2

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