Morpholine → N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl]-2-morpholin-4-yl-isonicotinamide

HRID 1611945Notes

Reaction equation

HRID 1611945 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][N:27]=1)[C:5]([NH:7][C:8]1[O:9][C:10]2[C:16]([CH: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].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>CN1CCCC1=O>[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:50]4[CH2:55][CH2:54][O:53][CH2:52][CH2:51]4)[CH:3]=3)[O:9][C:10]=2[C:16]([CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 314042,6-Di-tert-butyl-4-methylphenolHCID 222522322-bromo-N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl]-isonicotinamide

Product 1

HCID 22252243N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl]-2-morpholin-4-yl-isonicotinamideYield 29.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

A stirred suspension of 460 mg (1.06 mmol) 2-bromo-N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl]-isonicotinamide, 693 mg (2.13 mmol) cesium carbonate and a few crystals of 2,6-di-tert-butyl-p-cresol in 2.78 ml (3.19 mmol) morpholine and 2 ml N-methylpyrrolidone 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 (2/98 methanol/dichloromethane) followed by trituration in ether afforded 136 mg (29%) N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl]-2-morpholin-4-yl-isonicotinamide as a white crystalline solid. ES-MS m/e (%): 439 (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-f9d409ee2a2240268ce6da4b7717c9dc
Source dataset
uspto-grants-2006_01
Patent number
US06992083B2

Reaction notes

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