Methylamine → HCID 16723055, compound

HRID 1983167Notes

Reaction equation

HRID 1983167 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([C:13]3[C:14]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[N:15][O:16][C:17]=3[CH3:18])=[N:11][N:12]=2)=[C:4]([O:25][CH3:26])[CH:3]=1.Br[N:28]1C(=O)CC[C:29]1=O.N(C(C)(C)C#N)=NC(C)(C)C#N.CN.C(=O)([O-])[O-].[K+].[K+]>C(Cl)(Cl)(Cl)Cl.ClCCl.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([C:13]3[C:14]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[N:15][O:16][C:17]=3[CH2:18][NH:28][CH3:29])=[N:11][N:12]=2)=[C:4]([O:25][CH3:26])[CH:3]=1

Participants

9

Reactant 5

HCID 6329MethylamineHCID 6547AzobisisobutyronitrileHCID 11430Potassium CarbonateHCID 67184N-bromobutanimideHCID 167226452-(4-Fluoro-2-methoxy-phenyl)-5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazole

Product 1

HCID 16723055HCID 16723055, compoundYield 46%

Reagents, catalysts & solvents 3

HCID 5943Carbon TetrachlorideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2-(4-fluoro-2-methoxy-phenyl)-5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazole (241 mg, 0.69 mmol) in carbon tetrachloride (2 mL) was added N-bromosuccinimide (122 mg, 0.69 mmol) and 2,2′-azobis(2-methylpropionitrile) (11 mg, 0.07 mmol) and the reaction mixture was stirred for 18 h at 70° C. It was diluted with dichloromethane (10 mL) and washed with aqueous sodium hydrogencarbonate (1 N, 10 mL). The aqueous phase was extracted with dichloromethane and dried over sodium sulfate. The resulting crude material was suspended in methylamine solution (2 M in THF, 2.0 mL, 4.0 mmol) and potassium carbonate (110 mg, 0.80 mmol)was added. The reaction mixture was stirred for 2 h at 50° C. The mixture was diluted with ethyl acetate (20 ml), washed twice aqueous sodium carbonate (half saturated) and was extracted with ethyl acetate. Drying over sodium sulfate and purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane:methanol 40:40:20:0 to 0:75:20:5) afforded the tide compound (119 mg, 46%) as a white solid. MS: m/e 381.2 [M+H]+.

Workup

  1. washwashed with aqueous sodium hydrogencarbonate (1 N, 10 mL)
  2. extractionThe aqueous phase was extracted with dichloromethane
  3. dry with materialdried over sodium sulfate
  4. stirringThe reaction mixture was stirred for 2 h at 50° C
  5. washwashed twice aqueous sodium carbonate (half saturated)
  6. extractionwas extracted with ethyl acetate
  7. dry with materialDrying over sodium sulfate and purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane:methanol 40:40:20:0 to 0:75:20:5)

Sources & evidence

ORD record
ord-01101b80128542a58582b62ee957dde9
Source dataset
uspto-grants-2009_06
Patent number
US07541372B2

Reaction notes

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