Betahistine → N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-2-[methyl-(2-pyridin-2-yl-ethyl)-amino]-isonicotinamide

HRID 1167739Notes

Reaction equation

HRID 1167739 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][N:27]=1)[C:5]([NH:7][C:8]1[S:9][C:10]2[C:16]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:15][CH:14]=[C:13]([O:23][CH3:24])[C:11]=2[N:12]=1)=[O:6].[CH3:28][NH:29][CH2:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>>[CH3:24][O:23][C:13]1[C:11]2[N:12]=[C:8]([NH:7][C:5](=[O:6])[C:4]3[CH:25]=[CH:26][N:27]=[C:2]([N:29]([CH3:28])[CH2:30][CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=4)[CH:3]=3)[S:9][C:10]=2[C:16]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[CH:15][CH:14]=1

Participants

4

Reactant 3

HCID 2366BetahistineHCID 10796Cesium carbonateHCID 229934292-bromo-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-isonicotinamide

Product 1

HCID 10195983N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-2-[methyl-(2-pyridin-2-yl-ethyl)-amino]-isonicotinamideYield 71%

Conditions

Temperature
140 °C

Procedure

A stirred suspension of 200 mg (0.45 mmol) 2-bromo-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-isonicotinamide, 1.23 ml (8.90 mmol) 2-(2-methylaminoethyl)pyridine and 290 mg (0.89 mmol) cesium carbonate in a thick-walled glass pressure tube fitted with a teflon cap was heated at 140° C. for 24 h. The reaction mixture was then cooled to room temperature and poured onto water. The mixture was extracted three times with dichloromethane, and the combined organic phases were washed with saturated brine, dried over sodium sulfate, and concentrated in vacuo. Flash chromatography (0/100-2.5/97.5 methanol/dichlormoethane) followed by trituration in ether afforded 160 mg (71%) N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-2-[methyl-(2-pyridin-2-yl-ethyl)-amino]-isonicotinamide as a light yellow crystalline solid. ES-MS m/e (%): 505 (M+H+, 100).

Workup

  1. customcap
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. additionpoured onto water
  4. extractionThe mixture was extracted three times with dichloromethane
  5. washthe combined organic phases were washed with saturated brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ccc71cdd356044d89426b9c573344f17
Source dataset
uspto-grants-2003_09
Patent number
US06620811B2

Reaction notes

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