(1r)-3-[7-(Azidomethyl)-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 → (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

HRID 2224992Notes

Reaction equation

HRID 2224992 reaction equation
[N:1]([CH2:4][C:5]1[C:13]2[S:12](=[O:15])(=[O:14])[N:11]=[C:10]([C:16]3[C:17](=[O:34])[C@@:18]([CH2:28][CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:27])[C:19]4[C:24]([C:25]=3[OH:26])=[CH:23][CH:22]=[CH:21][CH:20]=4)[NH:9][C:8]=2[S:7][CH:6]=1)=[N+]=[N-]>C(O)C.[Pd]>[NH2:1][CH2:4][C:5]1[C:13]2[S:12](=[O:15])(=[O:14])[N:11]=[C:10]([C:16]3[C:17](=[O:34])[C@@:18]([CH2:28][CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:27])[C:19]4[C:24]([C:25]=3[OH:26])=[CH:23][CH:22]=[CH:21][CH:20]=4)[NH:9][C:8]=2[S:7][CH:6]=1

Participants

4

Reactant 1

HCID 137194540(1r)-3-[7-(Azidomethyl)-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 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)-oneYield 57.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A solution of Example 186A (17 mg, 0.03 mmol) in 2 mL of ethanol was degassed, treated with palladium on carbon (˜1 mg, 10%), put under an atmosphere of hydrogen, stirred for 4 h at room temp, filtered through a plug of celite, and concentrated to afford a yellow solid. The crude material was chromatographed on silica gel with a gradient of methanol in dichloromethane (0-10%) to afford the title compound (8.2 mg, 51% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.44 (m, 1 H) 0.70 (s, 9 H) 0.79 (m, 1 H) 1.39 (s, 3 H) 1.74 (m, J=3.31 Hz, 1 H) 2.15 (td, J=12.41, 4.23 Hz, 1 H) 4.12 (s, 2 H) 7.22 (s, 1 H) 7.33 (m, 1 H) 7.48 (m, 2 H) 8.04 (d, J=7.35 Hz, 1 H) 8.17 (br. s., 2 H) 16.99 (s, 1 H); MS (APCI+) m/z 474 (M+H)+.

Workup

  1. filtrationfiltered through a plug of celite
  2. concentrationconcentrated
  3. customto afford a yellow solid
  4. customThe crude material was chromatographed on silica gel with a gradient of methanol in dichloromethane (0-10%)

Sources & evidence

ORD record
ord-58c544c6d4444410b07d021018a05414
Source dataset
uspto-grants-2008_05
Patent number
US07378414B2

Reaction notes

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