(S)-(4-(3,4-Dichlorobenzyl)morpholin-2-YL)methanamine → n-{[(2s)-4-(3,4-Dichlorobenzyl)morpholin-2-yl]methyl}-2-[5-(4-fluorophenyl)-1,2,4oxadiazol-3-yl]acetamide

HRID 2212025Notes

Reaction equation

HRID 2212025 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH2:13][C:14]([O:16]C)=O)[N:9]=2)=[CH:4][CH:3]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:31]=[CH:32][C:33]=1[Cl:34])[CH2:22][N:23]1[CH2:28][CH2:27][O:26][C@@H:25]([CH2:29][NH2:30])[CH2:24]1>CN1CCCC1=O.CO>[Cl:18][C:19]1[CH:20]=[C:21]([CH:31]=[CH:32][C:33]=1[Cl:34])[CH2:22][N:23]1[CH2:28][CH2:27][O:26][C@@H:25]([CH2:29][NH:30][C:14](=[O:16])[CH2:13][C:10]2[N:9]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[O:12][N:11]=2)[CH2:24]1

Participants

5

Reactant 2

HCID 10171585(S)-(4-(3,4-Dichlorobenzyl)morpholin-2-YL)methanamineHCID 85817174Methyl (5-(4-fluorophenyl)-1,2,4-oxadiazol-3-yl]acetate

Product 1

HCID 68880198n-{[(2s)-4-(3,4-Dichlorobenzyl)morpholin-2-yl]methyl}-2-[5-(4-fluorophenyl)-1,2,4oxadiazol-3-yl]acetamideYield 57.4%

Reagents, catalysts & solvents 2

HCID 13387N-methyl-2-pyrrolidoneCatalystHCID 887MethanolSolvent2×

Procedure

A mixture of Intermediate 38 (0.024 g), Intermediate 9 (0.025 g), and 1-methyl-2-pyrrolidinone (1 drop) was subjected was subjected to irradiation in a 600 W microwave oven on full power for 4 mins. The reaction mixture was dissolved in methanol and applied to an ion exchange cartridge (2 g Isolute SCX, pre-conditioned with methanol). Elution with methanol (3 column volumes) followed 10% 0.880 ammonia in methanol (2 column volumes) and evaporation of the first basic fraction in vacuo gave the crude product. Purification by Biotage flash column chromatography on silica gel (8 g cartridge), eluting with 100:8:1 dichloromethane/ethanol/0.880 ammonia, gave the title compound as a white solid (0.025 g). LCMS (System A) Rf 2.85 min Mass Spectrum m/z 479, 481 [MH+]

Workup

  1. customwas subjected to irradiation in a 600 W microwave oven on full power for 4 mins
  2. washElution with methanol (3 column volumes)
  3. custom10% 0.880 ammonia in methanol (2 column volumes) and evaporation of the first basic fraction in vacuo
  4. customgave the crude product
  5. customPurification by Biotage flash column chromatography on silica gel (8 g cartridge)
  6. washeluting with 100:8:1 dichloromethane/ethanol/0.880 ammonia

Sources & evidence

ORD record
ord-b7237dedf4304fe6a8fdb8ecdd4c9e3c
Source dataset
uspto-grants-2006_09
Patent number
US07101882B2

Reaction notes

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