Acetic Acid → HCID 69491155, compound

HRID 1296746Notes

Reaction equation

HRID 1296746 reaction equation
C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH2:19][C:20]1[CH:40]=[C:39]([C:41]2[N:45]=C(C)O[N:42]=2)[CH:38]=[CH:37][C:21]=1[CH2:22][NH:23][C:24](=[O:36])[C:25]1[CH:30]=[C:29]([O:31][CH3:32])[C:28]([CH3:33])=[C:27]([O:34][CH3:35])[CH:26]=1.[CH3:47][C:48]([CH3:50])=O.COC(OC)OC>ClCCCl.CO.[Ni]>[C:41]([C:39]1[CH:38]=[CH:37][C:21]([CH2:22][NH:23][C:24](=[O:36])[C:25]2[CH:30]=[C:29]([O:31][CH3:32])[C:28]([CH3:33])=[C:27]([O:34][CH3:35])[CH:26]=2)=[C:20]([NH:19][CH:48]([CH3:50])[CH3:47])[CH:40]=1)(=[NH:42])[NH2:45]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 180AcetoneHCID 9005Trimethyl orthoformateHCID 5049666Sodium triacetoxyborohydrideHCID 69491883N-[2-Amino-4-(5-methyl-[1,2,4]oxadiazol-3-yl)-benzyl]-3,5-dimethoxy-4-methyl-benzamide

Product 1

HCID 69491155HCID 69491155, compound

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent2×

Procedure

Acetic acid (0.007 mL, 0.12 mmol) and sodium triacetoxyborohydride (42 mg, 0.20 mmol) were added to a suspension of compound 1g (50 mg, 0.13 mmol) and acetone (0.010 mL, 0.14 mmol) in DCE (0.5 mL). The reaction was stirred at rt for 16 h. Trimethylorthoformate (0.5 mL) was added, and the reaction was stirred at rt for 24 h. MeOH (1 mL) was added, and the reaction was stirred for 3 h. The reaction mixture was concentrated on a rotary evaporator and the residue was purified by preparative tlc (silica gel, 9:1 chloroform/methanol). This material was dissolved in a mixture of MeOH (3 mL) and TEA (0.040 mL, 0.29 mmol), and Raney nickel (washed with methanol) was added. The reaction mixture was hydrogenated overnight (50 psi), filtered, and concentrated on a rotary evaporator. The residue was purified by reverse phase HPLC (C18 column, water/acetonitrile gradient containing 0.1% TFA) to give to give Example 11. ESI-MS m/e 385.4 (M+1).

Workup

  1. stirringthe reaction was stirred at rt for 24 h
  2. stirringthe reaction was stirred for 3 h
  3. concentrationThe reaction mixture was concentrated on a rotary evaporator
  4. customthe residue was purified by preparative tlc (silica gel, 9:1 chloroform/methanol)
  5. additionwas added
  6. waitThe reaction mixture was hydrogenated overnight
  7. filtration(50 psi), filtered
  8. concentrationconcentrated on a rotary evaporator
  9. customThe residue was purified by reverse phase HPLC (C18 column, water/acetonitrile gradient containing 0.1% TFA)
  10. customto give
  11. customto give Example 11

Sources & evidence

ORD record
ord-348fb0e81fa94c2d8288ae3c9699f575
Source dataset
uspto-grants-2007_07
Patent number
US07247654B2

Reaction notes

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