Triethylamine → 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)methanesulfonamide

HRID 494673Notes

Reaction equation

HRID 494673 reaction equation
[NH2:1][CH2:2][C:3]1[C:11]2[S:10](=[O:13])(=[O:12])[N:9]=[C:8]([C:14]3[C:15](=[O:32])[C@@:16]([CH2:26][CH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:25])[C:17]4[C:22]([C:23]=3[OH:24])=[CH:21][CH:20]=[CH:19][CH:18]=4)[NH:7][C:6]=2[S:5][CH:4]=1.C(N(CC)CC)C.[CH3:40][S:41](Cl)(=[O:43])=[O:42]>CN(C)C=O.O>[CH3:29][C:28]([CH3:31])([CH3:30])[CH2:27][CH2:26][C@:16]1([CH3:25])[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:23]([OH:24])=[C:14]([C:8]2[NH:7][C:6]3[S:5][CH:4]=[C:3]([CH2:2][NH:1][S:41]([CH3:40])(=[O:43])=[O:42])[C:11]=3[S:10](=[O:13])(=[O:12])[N:9]=2)[C:15]1=[O:32]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 135953293(1r)-3-[7-(Aminomethyl)-1,1-dioxido-4h-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-1-(3,3-dimethylbutyl)-4-hydroxy-1-methylnaphthalen-2(1h)-one

Product 1

HCID 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)methanesulfonamideYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of Example 186B (168 mg, 0.36 mmol) in 3 mL of N,N-dimethyl formamide was cooled to 0° C., treated with triethylamine (90 μL, 0.82 mmol) and methanesulfonyl chloride (32 μL, 0.41 mmol), allowed to warm to room temp, stirred for 2 h, diluted with water, and extracted with ethyl acetate. The organic phase was washed with water and concentrated in vacuo to afford a yellow foam. The concentrate was purified on silica gel with a gradient of methanol in dichloromethane (0-2%) to afford the title compound (150 mg, 76% yield). 1H NMR (500 MHz, C6D6) δ ppm 0.40 (m, 1H) 0.72 (s, 9H) 0.82 (m, 1H) 1.55 (s, 3H) 2.01 (m, 1H) 2.21 (td, J=12.66, 3.97 Hz, 1H) 2.97 (s, 3H) 4.28 (d, J=5.49 Hz, 2H) 7.30 (s, 1H) 7.49 (m, 1H) 7.66 (t, J=6.10 Hz, 1H) 7.70 (s, 2H) 8.12 (d, J=7.32 Hz, 1H) 14.42 (m, 1H); MS (APCI−) m/z 550 (M−H)−.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phase was washed with water
  3. concentrationconcentrated in vacuo
  4. customto afford a yellow foam
  5. customThe concentrate was purified on silica gel with a gradient of methanol in dichloromethane (0-2%)

Sources & evidence

ORD record
ord-1271735a6f924c30a0264634fdfab5ef
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

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