Sulfuric Acid → HCID 66668753, compound

HRID 1618020Notes

Reaction equation

HRID 1618020 reaction equation
O/N=[C:3](/[C:22]1C=CN=C(C)C=1)\[CH2:4][C@H:5]([C:13]1[CH:21]=[CH:20][C:16]([C:17](O)=O)=[CH:15][CH:14]=1)[C:6]1C=CC=C[C:7]=1C.C([N:32]([CH:35]([CH3:37])[CH3:36])[CH2:33][CH3:34])(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:49]2N=[CH:51][CH:52]=[CH:53][C:48]=2N=N1.[C:62]([NH:65][NH2:66])(=[O:64])[CH3:63].S(=O)(=O)(O)[OH:68]>CN(C)C=O>[CH3:63][C:62]1[O:64][C:17]([C:16]2[CH:20]=[CH:21][C:13]([CH:5]([C:6]3[CH:7]=[CH:51][CH:52]=[CH:53][C:48]=3[CH3:49])[CH2:4][C:3]([C:22]3[CH:34]=[CH:33][N:32]=[C:35]([CH3:36])[CH:37]=3)=[O:68])=[CH:14][CH:15]=2)=[N:66][N:65]=1

Participants

7

Reactant 5

HCID 1118Sulfuric AcidHCID 14039AcetohydrazideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 136166999HCID 136166999, compound

Product 1

HCID 66668753HCID 66668753, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[(−)-3-(2-methyl-pyridin-4-yl)-3-oxo-1-o-tolyl-propyl]-benzoic acid (80 mg; example 272, step 2) and diisopropylethylamine (0.078 mL) in N,N-dimethylformamide (2.6 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (102 mg) and the reaction mixture stirred at room temperature. After 5 min, acetic acid hydrazide (35 mg; CAS RN 1068-57-1) was added and the reaction mixture heated by microwave irradiation to 100° C. for 10 min. To the reaction mixture was added conc. sulfuric acid (0.24 mL; strongly exothermic!) and heating by microwave irradiation at 140° C. continued for another 10 min. The reaction mixture was extracted over a sat. solution of sodium hydrogencarbonate (50 mL) with ethyl acetate (3×50 mL) and the combined organic phases dried over sodium sulfate. The crude reaction product was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane/ethyl acetate (100:0 to 50:50) to give the title compound as a light red oil. MS (ESI+): m/z=398.1 ([M+H]+).

Workup

  1. temperaturethe reaction mixture heated by microwave irradiation to 100° C. for 10 min
  2. temperature) and heating by microwave irradiation at 140° C.
  3. waitcontinued for another 10 min
  4. extractionThe reaction mixture was extracted over a sat. solution of sodium hydrogencarbonate (50 mL) with ethyl acetate (3×50 mL)
  5. dry with materialthe combined organic phases dried over sodium sulfate
  6. customThe crude reaction product
  7. customwas purified by silica gel chromatography
  8. washeluting with a gradient of n-heptane/ethyl acetate (100:0 to 50:50)

Sources & evidence

ORD record
ord-b3c6945781b54f95ae5f124a3a4cf3b4
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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