N-(tert-butoxycarbonyl)glycine → 2-{(2R)-4-[4-(5-aminomethyl-[1,2,4]oxadiazol-3-yl)-phenyl]-2-methyl-piperazin-1-yl}-1-methyl-1H-[4,4']bipyrimidinyl-6-one

HRID 1045697Notes

Reaction equation

HRID 1045697 reaction equation
C(OC([NH:8][CH2:9][C:10](O)=O)=O)(C)(C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[OH:55][NH:56][C:57](=[NH:85])[C:58]1[CH:63]=[CH:62][C:61]([N:64]2[CH2:69][CH2:68][N:67]([C:70]3[N:71]([CH3:83])[C:72](=[O:82])[CH:73]=[C:74]([C:76]4[CH:81]=[CH:80][N:79]=[CH:78][N:77]=4)[N:75]=3)[C@H:66]([CH3:84])[CH2:65]2)=[CH:60][CH:59]=1>CN(C)C=O.O>[NH2:8][CH2:9][C:10]1[O:55][N:56]=[C:57]([C:58]2[CH:59]=[CH:60][C:61]([N:64]3[CH2:69][CH2:68][N:67]([C:70]4[N:71]([CH3:83])[C:72](=[O:82])[CH:73]=[C:74]([C:76]5[CH:81]=[CH:80][N:79]=[CH:78][N:77]=5)[N:75]=4)[C@H:66]([CH3:84])[CH2:65]3)=[CH:62][CH:63]=2)[N:85]=1

Participants

8

Reactant 5

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27960291-Hydroxybenzotriazole hydrateHCID 178461498HCID 178461498, compound

Product 1

HCID 578701962-{(2R)-4-[4-(5-aminomethyl-[1,2,4]oxadiazol-3-yl)-phenyl]-2-methyl-piperazin-1-yl}-1-methyl-1H-[4,4']bipyrimidinyl-6-oneYield 27%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of N-tertbutoxycarbonylglycine (94 mg, 0.535 mmol) in N,N-dimethylformamide (2.0 ml) was added [2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumtetrafluoroborate (172 mg, 0.535 mmol), 1-hydroxybenzotriazole hydrate (14 mg, 0.107 mmol) and N,N-diisopropylethylamine (0.31 ml, 1.78 mmol), and the reaction mixture was stirred for 30 minutes at room temperature. After the addition of N-hydroxy-4-[(3R)-3-methyl-4-(1-methyl-6-oxo-1,6-dihydro-[4,4′]bipyrimidinyl-2-yl)-piperazin-1-yl]-benzamidine (145 mg, 0.356 mmol), the reaction mixture was stirred for one hour at room temperature, and then heated to 110° C. When the reaction was complete (checked by thin layer chromatography), excess reagent was decomposed by the addition of water and the aqueous layer was extracted with ethyl acetate. The extract was washed with water and brine, dried over magnesium sulfate, and concentrated in vacuo. The resulting residue was treated with trifluoroacetic acid, and the reaction mixture was stirred for 1 hour. After removal of the solvent, the residue was purified with HPLC to afford 2-{(2R)-4-[4-(5-aminomethyl-[1,2,4]oxadiazol-3-yl)-phenyl]-2-methyl-piperazin-1-yl}-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (44 mg, 0.096 mmol, 27%) as colorless crystals.

Workup

  1. stirringthe reaction mixture was stirred for one hour at room temperature
  2. temperatureheated to 110° C
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washThe extract was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. additionThe resulting residue was treated with trifluoroacetic acid
  8. stirringthe reaction mixture was stirred for 1 hour
  9. customAfter removal of the solvent
  10. customthe residue was purified with HPLC

Sources & evidence

ORD record
ord-58d5d3b5bcbc4ce19c63780d3767c95d
Source dataset
uspto-grants-2013_10
Patent number
US08569294B2

Reaction notes

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