Acetic Acid → HCID 25107026, compound

HRID 885114Notes

Reaction equation

HRID 885114 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[S:26][C:25]([C:27]3([OH:32])[CH2:31][CH2:30][NH:29][CH2:28]3)=[N:24][CH:23]=2)=[CH:18][CH:17]=1)=[O:14].[C:33](O)(=O)C.C=O>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:10])([F:11])[F:9])=[CH:4][C:3]=1[NH:12][C:13]([NH:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]2[S:26][C:25]([C:27]3([OH:32])[CH2:31][CH2:30][N:29]([CH3:33])[CH2:28]3)=[N:24][CH:23]=2)=[CH:20][CH:21]=1)=[O:14]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 712FormaldehydeHCID 25107025HCID 25107025, compound

Product 1

HCID 25107026HCID 25107026, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To an ambient solution of Example 14 (0.050 g, 0.107 mmol) in methanol containing 1% v/v acetic acid 1 mL) was added formaldehyde (0.012 mL, 0.161 mmol, 37 wt % in H2O) and MP-CNBH3 (0.054 g, 0.161 mmol, 3.0 mmol/g). The reaction was heated to 50° C. and shaken for 16 h. The reaction was then filtered and concentrated under reduced pressure. The residue was purified by RP-HPLC (preparative reversed-phase high pressure liquid chromatography) using a Zorbax SB-C18 7M 21.2×250 mm column with UV detection analyzed at 220 and 254 nM (preparative method: water with 0.1% trifluoroacetic acid and CH3CN with 0.1% trifluoroacetic acid gradient 5-95% CH3CN over 30 minutes at 15 mL/min). The fractions containing the desired product were diluted with saturated aqueous NaHCO3 and extracted with ethyl acetate. The organic layer was dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the title compound as a white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 2.01-2.13 (m, 1H), 2.25-2.33 (m, 3H), 2.35-2.46 (m, 1H), 2.51-2.58 (m, 1H), 2.73-2.94 (m, 3H), 6.22-6.31 (m, 1H), 7.37-7.44 (m, 1H), 7.47-7.56 (m, 3H), 7.56-7.62 (m, 2H), 7.98 (s, 1H), 8.62 (m, 1H), 8.92 (m, 1H), 9.32 (s, 1H); MS (ESI) m/z 481 [M+H]+.

Workup

  1. filtrationThe reaction was then filtered
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by RP-HPLC (preparative reversed-phase high pressure liquid chromatography)
  4. customanalyzed at 220 and 254 nM (preparative method: water with 0.1% trifluoroacetic acid and CH3CN with 0.1% trifluoroacetic acid gradient 5-95% CH3CN over 30 minutes at 15 mL/min)
  5. additionThe fractions containing the desired product
  6. additionwere diluted with saturated aqueous NaHCO3
  7. extractionextracted with ethyl acetate
  8. dry with materialThe organic layer was dried with anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ffae881c96c64c6d9a6f030d41996a67
Source dataset
uspto-grants-2012_08
Patent number
US08242139B2

Reaction notes

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