Diazepam → HCID 68650799, compound

HRID 646745Notes

Reaction equation

HRID 646745 reaction equation
[NH2:1][C:2]1[C:3]([C:18]([NH:20][CH3:21])=[O:19])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([NH:16][OH:17])=[NH:15])[CH:9]=2)=[CH:6][N:7]=1.CN1[C:30]2[CH:31]=[CH:32][C:33](Cl)=[CH:34][C:29]=2[C:28](C2C=CC=CC=2)=NCC1=O.C(Cl)(=O)C1C=CC=CC=1>CN(C=O)C.C(OCC)(=O)C>[NH2:1][C:2]1[C:3]([C:18]([NH:20][CH3:21])=[O:19])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[N:15]=[C:28]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[O:17][N:16]=3)[CH:9]=2)=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 3016DiazepamHCID 7412Benzoyl chlorideHCID 178485580HCID 178485580, compound

Product 1

HCID 68650799HCID 68650799, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Amino-N-methyl-6-{3-[(hydroxyamino)(imino)methyl]phenyl}pyrazine-2-carboxamide (40 mg, 0.14 mmol) was suspended in DMF (750 uL) followed by addition of PL-DIPAM (diisopropylaminomethyl) resin (100 mg, 2.33 mmol/g) and benzoyl chloride (20 uL, 0.17 mmol). The mixture was agitated for one hour then diluted with ethyl acetate and the spent resin removed by filtration, The organic filtrate was washed with water (3×), brine then dried over anhydrous magnesium sulfate. The mixture was then filtered and concentrated and the solid residue suspended in TIF (1 mmol) followed by addition of tetra-N-butylammonium fluoride (TBAF) (1.0 M in THF, 100 uL) and the solution was allowed to stir at room temperature over 12 hours. The mixture was concentrated and the residue partitioned with ethyl acetate and water. The organic layer was washed with water (1×), 1.0 M aqueous hydrochloric acid (lx) then brine and dried over anhydrous magnesium sulfate. The material was filtered and concentrated then the residue purified by preparative reverse phase HPLC (water/acetonitrile/0.1% TFA eluent). The pure fractions were combined and lyophilized to afford 3-amino-N-methyl-6-[3-(5-phenyl-1,2,4-oxadiazol-3-yl)phenyl]pyrazine-2-carboxamide (10.4 mg, 20% yield) as a yellow solid: MS (EI) for C20H17N6O2: 372 (MH+).

Workup

  1. customthe spent resin removed by filtration
  2. washThe organic filtrate was washed with water (3×), brine
  3. dry with materialthen dried over anhydrous magnesium sulfate
  4. filtrationThe mixture was then filtered
  5. concentrationconcentrated
  6. additionfollowed by addition of tetra-N-butylammonium fluoride (TBAF) (1.0 M in THF, 100 uL)
  7. stirringto stir at room temperature over 12 hours
  8. concentrationThe mixture was concentrated
  9. customthe residue partitioned with ethyl acetate and water
  10. washThe organic layer was washed with water (1×), 1.0 M aqueous hydrochloric acid (lx)
  11. dry with materialbrine and dried over anhydrous magnesium sulfate
  12. filtrationThe material was filtered
  13. concentrationconcentrated
  14. customthe residue purified by preparative reverse phase HPLC (water/acetonitrile/0.1% TFA eluent)

Sources & evidence

ORD record
ord-78947b7765614a4e957966180ee0f2a7
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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