Diisopropylethylamine → HCID 44252606、化合物

HRID 19119ノート

反応式

HRID 19119 の反応式
[CH2:1]([O:3][C:4]1[C:5]([F:26])=[C:6]([C:22]([F:25])=[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](O)=[O:15])[C:10](=[O:21])[CH:9]=1)[CH3:2].[CH3:27][C:28]1([CH3:40])[O:32][C@H:31]([CH2:33][N:34]2[CH:38]=[CH:37][C:36]([NH2:39])=[N:35]2)[CH2:30][O:29]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>CN(C)C=O>[CH3:27][C:28]1([CH3:40])[O:32][C@H:31]([CH2:33][N:34]2[CH:38]=[CH:37][C:36]([NH:39][C:14](=[O:15])[C@@H:13]([N:11]3[CH2:12][C:8]([O:7][C:6]4[C:22]([F:25])=[CH:23][CH:24]=[C:4]([O:3][CH2:1][CH3:2])[C:5]=4[F:26])=[CH:9][C:10]3=[O:21])[CH2:17][CH:18]([CH3:19])[CH3:20])=[N:35]2)[CH2:30][O:29]1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amineHCID 66893716(S)-2-[4-(3-ethoxy-2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid

生成物 1

HCID 44252606HCID 44252606、化合物収率 95%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a solution of (S)-2-[4-(3-ethoxy-2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (0.837 g, 2.27 mmol) in N,N-dimethylformamide (50 mL) was added 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 0.559 g, 2.83 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (1.505 g, 3.40 mmol). The mixture was stirred at 0° C. and N,N-diisopropylethylamine (0.732 g, 5.66 mmol) was added. The mixture was stirred at room temperature overnight 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 40 g, 50% to 90% ethyl acetate/hexanes) which afforded (S)-2-[4-(3-ethoxy-2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (1.180 g, 95%) as a pale yellow solid: HR-ES-MS m/z calculated for C27H34F2N4O6 [M+H]+ 549.2519, observed 549.2514, 1H NMR (300 MHz, DMSO-d6) δ ppm 1.00 0.90 (d, J=6.4 Hz, 3H), 0.93 (d, J=6.4 Hz, 3H), 1.25 (s, 3H), 1.30 (s, 3H), 1.35 (t, J=6.9 Hz, 3H), 1.38-1.49 (m, 1H), 1.50-1.67 (m, 1H), 1.68-1.84 (m, 1H), 3.73 (dd, J=8.5, 6.0 Hz, 1H), 3.96-4.19 (m, 5H), 4.27 (d, J=18.7 Hz, 1H), 4.31-4.40 (m, 1H), 4.63 (d, J=18.7 Hz, 1H), 4.88 (dd, J=10.7, 4.7 Hz, 1H), 5.06 (s, 1H), 6.43 (d, J=2.1 Hz, 1H), 7.11-7.22 (m, 1H), 7.27 (dt, J=9.7, 1.5 Hz, 1H), 7.60 (d, J=2.1 Hz, 1H), 10.82 (s, 1H).

後処理

  1. stirringThe mixture was stirred at room temperature overnight
  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 40 g, 50% to 90% ethyl acetate/hexanes) which

出典と根拠

ORDレコード
ord-f0c40e8ec1774baa97f7aeae7f0b3bd2
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

反応ノート

読み込み中…