Ethanol → (2S)-4-[6-fluoro-1-(2-fluorophenyl)-2,2-dioxido-1,4-dihydro-3H-2,1,3-benzothiadiazin-3-yl]-1-(methylamino)butan-2-ol

HRID 2237508Notes

Reaction equation

HRID 2237508 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[F:17])[S:9](=[O:19])(=[O:18])[N:8]([CH2:20][CH2:21][C@H:22]3[CH2:24][O:23]3)[CH2:7][C:6]=2[CH:25]=1.C(O)C.[CH3:29][NH2:30]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[F:17])[S:9](=[O:18])(=[O:19])[N:8]([CH2:20][CH2:21][C@H:22]([OH:23])[CH2:24][NH:30][CH3:29])[CH2:7][C:6]=2[CH:25]=1

Participants

4

Reactant 3

HCID 702EthanolHCID 6329MethylamineHCID 866211456-fluoro-1-(2-fluorophenyl)-3-{2-[(2S)-oxiran-2-yl]ethyl}-3,4-dihydro-1H-2,1,3-benzothiadiazine 2,2-dioxide

Product 1

HCID 25030268(2S)-4-[6-fluoro-1-(2-fluorophenyl)-2,2-dioxido-1,4-dihydro-3H-2,1,3-benzothiadiazin-3-yl]-1-(methylamino)butan-2-olYield 83%

Conditions

Temperature
100 °C

Procedure

6-fluoro-1-(2-fluorophenyl)-3-{2-[(2S)-oxiran-2-yl]ethyl}-3,4-dihydro-1H-2,1,3-benzothiadiazine 2,2-dioxide (0.12 g, 0.29 mmol) was dissolved in an 8 M solution of methylamine in ethanol (3 mL, 24 mmol) and was heated to 100° C. for 192 sec. in the microwave. The reaction mixture was evaporated and the residue purified by flash chromatography (SiO2, 0-5% 7 M NH3-methanol/dichloromethane). The purified free-base was dissolved in dichloromethane (3 mL) and treated with hydrogen chloride (1.0 mL of a 2 M solution in ethyl ether), resulting in a white precipitate that was evaporated and dried under vacuum to provide (2S)-4-[6-fluoro-1-(2-fluorophenyl)-2,2-dioxido-1,4-dihydro-3H-2,1,3-benzothiadiazin-3-yl]-1-(methylamino)butan-2-ol (0.10 g. 83%) as a white solid.

Workup

  1. customThe reaction mixture was evaporated
  2. customthe residue purified by flash chromatography (SiO2, 0-5% 7 M NH3-methanol/dichloromethane)
  3. dissolutionThe purified free-base was dissolved in dichloromethane (3 mL)
  4. additiontreated with hydrogen chloride (1.0 mL of a 2 M solution in ethyl ether),
  5. customresulting in a white precipitate that
  6. customwas evaporated
  7. customdried under vacuum

Sources & evidence

ORD record
ord-964138d9a4074ace8faf540118bd450d
Source dataset
uspto-grants-2010_05
Patent number
US07718652B2

Reaction notes

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