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 711347Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 711347
[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

Komponenten

4

Edukt 2

HCID 31297Methanesulfonyl chlorideHCID 118492002HCID 118492002, Verbindung

Produkt 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)-carboxamideAusbeute 23 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

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]+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-79e2d6e4975247009d8991a3d67627db
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09181259B2

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