1-Hydroxybenzotriazole → HCID 178481312, compound

HRID 1009499Notes

Reaction equation

HRID 1009499 reaction equation
C(OC([C@H:8]1[NH:13][C:12]([CH3:17])([C:14]([OH:16])=O)[CH2:11][C:10](=[O:18])[N:9]1[CH3:19])=O)(C)(C)C.C[N:21](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.O[N:62]=[C:63]([NH2:74])[C:64]1[CH:69]=[CH:68][CH:67]=[C:66]([C:70]([F:73])([F:72])[F:71])[CH:65]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CN(C=O)C.CCOC(C)=O>[NH:21]=[C:8]1[N:9]([CH3:19])[C:10](=[O:18])[CH2:11][C@@:12]([CH3:17])([C:14]2[O:16][N:74]=[C:63]([C:64]3[CH:69]=[CH:68][CH:67]=[C:66]([C:70]([F:73])([F:72])[F:71])[CH:65]=3)[N:62]=2)[NH:13]1

Participants

9

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 609330N'-hydroxy-3-(trifluoromethyl)benzimidamideHCID 2724141Tetrabutylammonium FluorideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67304181HCID 67304181, compound

Product 1

HCID 178481312HCID 178481312, compoundYield 35.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of (S)-2-(tert-butoxycarbonyl)-1,4-dimethyl-6-oxo-hexahydropyrimidine-4-carboxylic acid (CX2, R6=Me, 0.035 g, 0.12 mmol) in DMF (0.24 mL) was added TBTU (0.040 mg, 0.12 mmol, 1 eq), HOBt (0.0035 mg, 0.024 mmol, 0.2 eq), and DIEA (0.107 mL, 0.60 mmol, 5 eq). The mixture was stirred at RT for 10 min and then N′-hydroxy-3-(trifluoromethyl)benzamidine (0.028 mg, 0.13 mmol, 1.1 eq) was added. After stirring for another 2 h, the reaction mixture was diluted with EtOAc (20 mL), washed with H2O (10 mL) and saturated brine (10 mL), and concentrated in vacuo. The crude residue was dissolved in THF (0.4 mL) and then TBAF (1M in THF, 0.099 mL, 0.9 eq) was added. The mixture was stirred at RT for 2 h. EtOAc (20 mL) was added to the reaction mixture, which was washed with H2O (10 mL) and saturated brine (10 mL), and concentrated in vacuo. The residue was treated with 30% TFA/DCM (1 mL) at RT for 1. The reaction mixture was concentrated in vacuo and the crude product was purified on reverse phase HPLC (B) to give 0.015 g (26%) of (6S)-2-imino-3,6-dimethyl-6-(3-(3-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)-tetrahydropyrimidin-4(1H)-one (CX3; R6=Me, R7=3-(3-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)) as a white solid. 1H NMR (CD3OD): 8.40 (m, 2H), 8.04 (d, 1H, J=6.9 Hz), 7.90 (t, 1H, J=8.1 Hz), 3.81 (m, 2H), 3.39 (s, 3H), 1.82 (s, 3H). MS (ESI): MH+=354.2, HPLC (A) Rt=6.234 min.

Workup

  1. stirringAfter stirring for another 2 h
  2. washwashed with H2O (10 mL) and saturated brine (10 mL)
  3. concentrationconcentrated in vacuo
  4. dissolutionThe crude residue was dissolved in THF (0.4 mL)
  5. stirringThe mixture was stirred at RT for 2 h
  6. washwas washed with H2O (10 mL) and saturated brine (10 mL)
  7. concentrationconcentrated in vacuo
  8. additionThe residue was treated with 30% TFA/DCM (1 mL) at RT for 1
  9. concentrationThe reaction mixture was concentrated in vacuo
  10. customthe crude product was purified on reverse phase HPLC (B)

Sources & evidence

ORD record
ord-447c32edc9c8468f9a7ecd46e2dbbf16
Source dataset
uspto-grants-2011_07
Patent number
US07973067B2

Reaction notes

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