Diisopropylethylamine → (S)-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-(tetrahydro-furan-2-yl)-propionamide

HRID 18971

反応式

HRID 18971 の反応式
[CH3:1][O:2][C:3]1[CH:25]=[CH:24][CH:23]=[CH:22][C:4]=1[O:5][C:6]1[CH2:10][N:9]([C@@H:11]([CH2:15][CH:16]2[CH2:20][CH2:19][CH2:18][O:17]2)[C:12](O)=[O:13])[C:8](=[O:21])[CH:7]=1.[NH2:26][C:27]1[CH:31]=[CH:30][N:29]([CH2:32][C:33]([CH3:36])([OH:35])[CH3:34])[N:28]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>ClCCl>[OH:35][C:33]([CH3:36])([CH3:34])[CH2:32][N:29]1[CH:30]=[CH:31][C:27]([NH:26][C:12](=[O:13])[C@@H:11]([N:9]2[CH2:10][C:6]([O:5][C:4]3[CH:22]=[CH:23][CH:24]=[CH:25][C:3]=3[O:2][CH3:1])=[CH:7][C:8]2=[O:21])[CH2:15][CH:16]2[CH2:20][CH2:19][CH2:18][O:17]2)=[N:28]1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-olHCID 66894382(S)-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-(tetrahydro-furan-2-yl)-propionic acid

生成物 1

HCID 57920053(S)-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-(tetrahydro-furan-2-yl)-propionamide収率 36%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
25 °C

実験手順

A solution of (S)-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-(tetrahydro-furan-2-yl)-propionic acid (90 mg, 0.26 mmol) in dichloromethane (10 mL) was treated with 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 45 mg, 0.29 mmol), Benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (140 mg, 0.31 mmol) and N,N-diisopropylethylamine (100 mg, 0.78 mmol). The reaction mixture was stirred for 18 h at 25° C., under nitrogen. The reaction mixture was diluted with dichloromethane, washed with 2N aqueous hydrochloric acid, saturated sodium bicarbonate solution, saturated sodium chloride solution and dried over magnesium sulfate. The organic layer was concentrated, and the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 10% methanol/dichloromethane) to afford (S)-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-(tetrahydro-furan-2-yl)-propionamide (45 mg, 36%) as a yellow solid: LR-ES-MS m/z calculated for C25H32N4O6 [M]+ 484, observed [M+H]+ 485; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.05 (br. s., 3H) 1.06 (br. s., 3H) 1.35-2.11 (m, 6H) 3.54-3.79 (m, 3H) 3.81 (s, 3H) 3.89 (s, 2H) 4.18, 4.22 (2×d, J=18.0, 1H) 4.45 (d, J=18.0 Hz, 1H) 4.68 (s, 1H) 4.70 (s, 1H) 4.77-4.91 (m, 1H) 6.40-6.48 (m, 1H) 6.95-7.06 (m, 1H) 7.18-7.25 (m, 1H) 7.25-7.36 (m, 2H) 7.51-7.56 (m, 1H) 10.70, 10.73 (2×s, 1H).

後処理

  1. washwashed with 2N aqueous hydrochloric acid, saturated sodium bicarbonate solution, saturated sodium chloride solution
  2. dry with materialdried over magnesium sulfate
  3. concentrationThe organic layer was concentrated
  4. customthe crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 10% methanol/dichloromethane)

出典と根拠

ORDレコード
ord-903e8632c9fb4d28907c9b5afa33b0dd
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

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