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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
ノート
印刷プレビュー

反応式

HRID 19376 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 66895240HCID 66895240、化合物HCID 66899094HMS5552 HCl

生成物 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
収率 30%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-ffd37df479c14c65923be94202df6ca8
出典データセット
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07741327B2

反応ノート

読み込み中…

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