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 711347노트

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HRID 711347 반응식
[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

참가 물질

4

반응물 2

HCID 31297Methanesulfonyl chlorideHCID 118492002HCID 118492002, 화합물

생성물 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)-carboxamide수율 23%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
65 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-79e2d6e4975247009d8991a3d67627db
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181259B2

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