Methanesulfonyl chloride → (1'S,8a'S)-N-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethyl)-N-methyl-6'-oxo-1'-o-tolyloctahydro-1'H-spiro[pyran-4,7'-pyrrolo[1,2-a]pyrazine]-2'(6'H)-carboxamide

HRID 711347ノート

反応式

HRID 711347 の反応式
[F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:41])[C:16]([N:18]2[CH2:23][CH2:22][N:21]3[C:24](=[O:33])[C:25]([CH2:30][CH2:31]O)([CH2:27][CH2:28][OH:29])[CH2:26][C@H:20]3[C@@H:19]2[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[CH3:40])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CS(Cl)(=O)=O>C(Cl)Cl>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]([N:15]([CH3:41])[C:16]([N:18]2[CH2:23][CH2:22][N:21]3[C:24](=[O:33])[C:25]4([CH2:30][CH2:31][O:29][CH2:28][CH2:27]4)[CH2:26][C@H:20]3[C@@H:19]2[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[CH3:40])=[O:17])[CH3:14])[CH:4]=[C:3]([C:2]([F:1])([F:42])[F:43])[CH:8]=1

参加物

4

反応物 2

HCID 31297Methanesulfonyl chlorideHCID 118492002HCID 118492002、化合物

生成物 1

HCID 71715312(1'S,8a'S)-N-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethyl)-N-methyl-6'-oxo-1'-o-tolyloctahydro-1'H-spiro[pyran-4,7'-pyrrolo[1,2-a]pyrazine]-2'(6'H)-carboxamide収率 23%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
65 °C

実験手順

To a solution of (1S,8aS)-N-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethyl)-7,7-bis(2-hydroxyethyl)-N-methyl-6-oxo-1-o-tolylhexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxamide (70 mg, 0.11 mmol) in 5 mL of DCM, was added MsCl (38 mg, 0.33 mmol) at 0° C. The mixture was stirred for 1.5 h, and concentrated in high vacuum. The residue was treated with mixture of H2O (5 mL) and TEA (0.5 mL) and then heated to 65° C. until the reaction was completed. The reaction mixture was extracted with DCM (2×15 mL) and the organic layers were dried over anhydrous Na2Sa4 and then concentrated in high vacuum. The residue was purified by Prep-HPLC to give the title compound (15 mg, yield: 23%). 1H NMR (400 MHz, CDCl3) δ ppm 7.71 (s, 1H), 7.46 (s, 2H), 7.22 (m, 4H), 5.47 (d, J=7.0 Hz, 1H), 4.08 (d, J=12.8 Hz, 1H), 3.95 (d, J=9.7 Hz, 2H), 3.81 (dd, J=7.6, 4.0 Hz, 1H), 3.65 (d, J=9.1 Hz, 1H), 3.36 (dd, J=13.4, 6.3 Hz, 2H), 3.20 (d, J=11.6 Hz, 1H), 3.05 (td, J=12.3, 3.4 Hz, 1H), 2.91 (dt, J=11.8, 5.9 Hz, 1H), 2.63 (s, 3H), 2.46 (s, 3H), 2.11 (dd, J=17.6, 6.9 Hz, 1H), 1.89 (dd, J=13.1, 7.2 Hz, 1H), 1.79 (dd, J=17.0, 7.0 Hz, 1H), 1.49 (s, 2H), 1.31 (t, J=8.1 Hz, 6H), 1.18 (s, 3H), 0.86 (s, 2H); m/z (ES+): 598 [M+H]+.

後処理

  1. concentrationconcentrated in high vacuum
  2. additionThe residue was treated with mixture of H2O (5 mL) and TEA (0.5 mL)
  3. extractionThe reaction mixture was extracted with DCM (2×15 mL)
  4. customthe organic layers were dried over anhydrous Na2Sa4
  5. concentrationconcentrated in high vacuum
  6. customThe residue was purified by Prep-HPLC

出典と根拠

ORDレコード
ord-79e2d6e4975247009d8991a3d67627db
出典データセット
uspto-grants-2015_11
特許番号
US09181259B2

反応ノート

読み込み中…