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

HRID 985790Notes

Reaction equation

HRID 985790 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]([CH:17]3[CH2:22][O:21][CH2:20][CH2:19][O:18]3)=[CH:15][CH:14]=[C:13]([O:23][CH3:24])[C:11]=2[N:12]=1)=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].C(C1C(O)=C(C(C)(C)C)C=C(C)C=1)(C)(C)C.[NH:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1>>[O:18]1[CH2:19][CH2:20][O:21][CH2:22][CH:17]1[C:16]1[C:10]2[S:9][C:8]([NH:7][C:5](=[O:6])[C:4]3[CH:25]=[CH:26][N:27]=[C:2]([N:50]4[CH2:55][CH2:54][O:53][CH2:52][CH2:51]4)[CH:3]=3)=[N:12][C:11]=2[C:13]([O:23][CH3:24])=[CH:14][CH:15]=1

Participants

5

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 314042,6-Di-tert-butyl-4-methylphenolHCID 22507693(+)-2-bromo-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-isonicotinamide

Product 1

HCID 11419702(+)-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-2-morpholin-4-yl-isonicotinamideYield 43.1%

Conditions

Temperature
140 °C

Procedure

A stirred suspension of 150 mg (0.33 mmol) (±)-2-bromo-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-isonicotinamide, 217 mg (0.67 mmol) cesium carbonate and a few crystals of 2,6-di-tert-butyl-p-cresol in 2.90 ml (3.33 mmol) morpholine 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 ethyl acetate, and the combined organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (ethyl acetate) followed by trituration in ether afforded 65 mg (43%) (±)-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-2-morpholin-4-yl-isonicotinamide as a light yellow solid. ES-MS m/e (%): 457 (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 ethyl acetate
  5. dry with materialthe combined organic phases were dried over sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-264dc930eac04fcf9549a91abbf55eaa
Source dataset
uspto-grants-2005_03
Patent number
US06872833B2

Reaction notes

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