Acetic Acid → HCID 18433570, compound

HRID 2306229Notes

Reaction equation

HRID 2306229 reaction equation
[NH2:1][CH:2]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]2[CH:13]=[C:12]([O:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:11]=[CH:10][C:9]=2[Br:19])[C:3]1=[O:20].[C:21]([C:23]1[CH:36]=[CH:35][C:26]([CH2:27][N:28]2[C:32]([CH:33]=O)=[CH:31][N:30]=[CH:29]2)=[CH:25][C:24]=1[F:37])#[N:22].C(O)(=O)C.[BH3-]C#N.[Na+]>CO>[Br:19][C:9]1[CH:10]=[CH:11][C:12]([O:14][S:15]([CH3:18])(=[O:17])=[O:16])=[CH:13][C:8]=1[CH2:7][N:4]1[CH2:5][CH2:6][CH:2]([NH:1][CH2:33][C:32]2[N:28]([CH2:27][C:26]3[CH:35]=[CH:36][C:23]([C:21]#[N:22])=[C:24]([F:37])[CH:25]=3)[CH:29]=[N:30][CH:31]=2)[C:3]1=[O:20]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 114247081-(4-Cyano-3-fluorobenzyl)-5-imidazolecarboxaldehydeHCID 18433500HCID 18433500, compound

Product 1

HCID 18433570HCID 18433570, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-Amino-1-(2-bromo-5-methanesulfonyloxybenzyl)-2-oxopyrrolidine, as described above in Step E, (640 mg, 1.12 mmol), 1-(4-cyano-3-fluorobenzyl)-5-imidazolecarboxaldehyde, as described above in Example 1, Step G, (333 mg, 1.45 mmol) were stirred in MeOH (8 mL) and the solution was acidified to pH≈5 to 6, as judged by wetted pH indicator paper, with acetic acid. Stirring was continued for 30 min, then NaCNBH3 (118 mg, 1.88 mmol) was added. Stirring was continued for 18 hours, then the reaction was quenched with saturated aqueous NaHCO3 (2 mL) and most of the MeOH was removed under reduced pressure. The residual solution was partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (20 mL). The aqueous layer was extracted further with EtOAc (2×20 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica, eluting with a gradient of CH2Cl2—1% to 5% MeOH, to yield the desired product.

Workup

  1. stirringStirring
  2. waitwas continued for 18 hours
  3. customthe reaction was quenched with saturated aqueous NaHCO3 (2 mL) and most of the MeOH
  4. customwas removed under reduced pressure
  5. customThe residual solution was partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (20 mL)
  6. extractionThe aqueous layer was extracted further with EtOAc (2×20 mL)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by flash column chromatography on silica
  12. washeluting with a gradient of CH2Cl2—1% to 5% MeOH

Sources & evidence

ORD record
ord-07f1cf79c6814d96a03b182cfda13700
Source dataset
uspto-grants-2002_08
Patent number
US06441017B1

Reaction notes

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