Hydrochloric Acid → n-({3-[(4r)-4-(3,3-Dimethylbutyl)-1-hydroxy-4-methyl-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-thieno [2,3-e][1,2,4]thiadiazin-7-yl}methyl)-n-methylmethanesulfonamide

HRID 2224994Notes

Reaction equation

HRID 2224994 reaction equation
[CH3:1][C:2]([CH3:36])([CH3:35])[CH2:3][CH2:4][C@:5]1([CH3:34])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([OH:15])=[C:7]([C:16]2[NH:21][C:20]3[S:22][CH:23]=[C:24]([CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[C:19]=3[S:18](=[O:32])(=[O:31])[N:17]=2)[C:6]1=[O:33].[H-].[Na+].[CH3:39]I.Cl>CN(C)C=O.O.C(OCC)(=O)C>[CH3:1][C:2]([CH3:36])([CH3:35])[CH2:3][CH2:4][C@:5]1([CH3:34])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([OH:15])=[C:7]([C:16]2[NH:21][C:20]3[S:22][CH:23]=[C:24]([CH2:25][N:26]([CH3:39])[S:27]([CH3:30])(=[O:29])=[O:28])[C:19]=3[S:18](=[O:32])(=[O:31])[N:17]=2)[C:6]1=[O:33]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodide2×HCID 24758Sodium hydrideHCID 136384561n-({3-[(4r)-4-(3,3-Dimethylbutyl)-1-hydroxy-4-methyl-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-thieno [2,3-e][1,2,4]thiadiazin-7-yl}methyl)methanesulfonamide

Product 1

HCID 135903316n-({3-[(4r)-4-(3,3-Dimethylbutyl)-1-hydroxy-4-methyl-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-thieno [2,3-e][1,2,4]thiadiazin-7-yl}methyl)-n-methylmethanesulfonamideYield 60.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of Example 187 (124 mg, 0.22 mmol) in 2 mL of N,N-dimethyl formamide was cooled to 0° C., treated with sodium hydride (24 mg, 60% in oil, 0.5 mmol), stirred at 0° C. for 1 h, stirred at room temp for 30 min, treated with methyl iodide (9 μL, 0.14 mmol), stirred for 2 h, treated with methyl iodide (7 μL, 0.11 mmol), and stirred at room temp over night. The mixture was diluted with water and ethyl acetate, treated with 1N HCl, and extracted with ethyl acetate. The organic phase was washed with 2×10 mL of H2O and concentrated in vacuo. The crude material was chromatographed on silica gel with a gradient of methanol in dichloromethane (0-5%) to afford the title compound (48 mg, 39% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 0.40 (td, J=12.8, 3.7 Hz, 1 H), 0.72 (s, 9 H), 0.81 (td, J=12.9, 4.4 Hz, 1 H), 1.56 (s, 3 H), 2.01 (m, 1 H), 2.21 (td, J=12.8, 4.6 Hz, 1 H), 2.85 (s, 3 H), 3.02 (s, 3 H), 4.39 (s, 2 H), 7.32 (s, 1 H), 7.50 (m, 1 H), 7.71 (m, 2 H), 8.12 (d, J=7.8 Hz, 1 H), 14.21 (s, 1 H); MS (APCI−) m/z 564 (M−H)−.

Workup

  1. stirringstirred at room temp for 30 min
  2. stirringstirred for 2 h
  3. stirringstirred at room temp over night
  4. extractionextracted with ethyl acetate
  5. washThe organic phase was washed with 2×10 mL of H2O
  6. concentrationconcentrated in vacuo
  7. customThe crude material was chromatographed on silica gel with a gradient of methanol in dichloromethane (0-5%)

Sources & evidence

ORD record
ord-5289d036e0ce440e96821666c3fc370b
Source dataset
uspto-grants-2008_05
Patent number
US07378414B2

Reaction notes

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