Sodium hydride → (+)-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-2-(2-morpholin-4-yl-ethoxy)-isonicotinamide

HRID 985841Notes

Reaction equation

HRID 985841 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.C(C1C(O)=C(C(C)(C)C)C=C(C)C=1)(C)(C)C.[H-].[Na+].Br[C:29]1[CH:30]=[C:31]([CH:52]=[CH:53][N:54]=1)[C:32]([NH:34][C:35]1[S:36][C:37]2[C:43]([CH:44]3[CH2:49][O:48][CH2:47][CH2:46][O:45]3)=[CH:42][CH:41]=[C:40]([O:50][CH3:51])[C:38]=2[N:39]=1)=[O:33]>O1CCOCC1.CN(C=O)C>[O:45]1[CH2:46][CH2:47][O:48][CH2:49][CH:44]1[C:43]1[C:37]2[S:36][C:35]([NH:34][C:32](=[O:33])[C:31]3[CH:52]=[CH:53][N:54]=[C:29]([O:1][CH2:2][CH2:3][N:4]4[CH2:9][CH2:8][O:7][CH2:6][CH2:5]4)[CH:30]=3)=[N:39][C:38]=2[C:40]([O:50][CH3:51])=[CH:41][CH:42]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 314042,6-Di-tert-butyl-4-methylphenolHCID 611632-MorpholinoethanolHCID 22507693(+)-2-bromo-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-isonicotinamide

Product 1

HCID 11466172(+)-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-2-(2-morpholin-4-yl-ethoxy)-isonicotinamideYield 72.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 437 mg (3.33 mmol) N-(2-hydroxyethyl)morpholine and 20 mg (0.09 mmol) 2,6-di-tert-butyl-para-cresol in 5 ml dioxane and 1 ml DMF was added portionwise 194 mg (4.44 mmol) sodium hydride (55% dispersion in oil) and the mixture heated at 50° C. for 30 min. 200 mg (0.44 mmol) (+)-2-bromo-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-isonicotinamide was then added and the mixture heated at 80° C. for 16 h. The reaction mixture was then poured onto water and extracted three times with ethyl acetate. The organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (5/95 methanol/ethyl acetate) followed by trituration in ether and hexane afforded 160 mg (72%) (+)-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-2-(2-morpholin-4-yl-ethoxy)-isonicotinamide as a white solid. [α]D20=+51.2° (c=1.04, CHCl3), ES-MS m/e (%): 501 (M+H+, 100).

Workup

  1. temperaturethe mixture heated at 80° C. for 16 h
  2. additionThe reaction mixture was then poured onto water
  3. extractionextracted three times with ethyl acetate
  4. dry with materialThe organic phases were dried over sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8bd822afff494e75907b333e06315284
Source dataset
uspto-grants-2005_03
Patent number
US06872833B2

Reaction notes

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