Methanesulfonyl chloride → HCID 71715312, compound

HRID 711347Notes

Reaction equation

HRID 711347 reaction equation
[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

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 118492002HCID 118492002, compound

Product 1

HCID 71715312HCID 71715312, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-79e2d6e4975247009d8991a3d67627db
Source dataset
uspto-grants-2015_11
Patent number
US09181259B2

Reaction notes

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