Formaldehyde → HCID 178479847, compound

HRID 2373522Notes

Reaction equation

HRID 2373522 reaction equation
C([O:9][C:10]1[C:11]([OH:37])=[N:12][C:13]([C:20]23[N:26]([C:27](OCC4C=CC=CC=4)=O)[CH:23]([CH2:24][CH2:25]2)[CH2:22][CH2:21]3)=[N:14][C:15]=1[C:16]([O:18]C)=O)(=O)C1C=CC=CC=1.[F:38][C:39]1[CH:46]=[CH:45][C:42]([CH2:43][NH2:44])=[CH:41][CH:40]=1.[BH3-]C#N.[Na+].C(O[Na])(C)=O.C=O>CO.[Pd]>[F:38][C:39]1[CH:46]=[CH:45][C:42]([CH2:43][NH:44][C:16]([C:15]2[C:10]([OH:9])=[C:11]([OH:37])[N:12]=[C:13]([C:20]34[N:26]([CH3:27])[CH:23]([CH2:22][CH2:21]3)[CH2:24][CH2:25]4)[N:14]=2)=[O:18])=[CH:41][CH:40]=1

Participants

8

Reactant 5

HCID 712FormaldehydeHCID 673264-FluorobenzylamineHCID 5003444Sodium cyanoborohydrideHCID 178418247HCID 178418247, compoundHCID 178499059HCID 178499059, compound

Product 1

HCID 178479847HCID 178479847, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Benzyl 1-[5-(benzoyloxy)-4-hydroxy-6-(methoxycarbonyl)pyrimidin-2-yl]-7-azabicyclo[2.2.1]heptane-7-carboxylate (C-39) in methanol was hydrogenated under H2 atmosphere in presence of Pd/C 10% (10% w/w) at room temperature for 2 hours. After filtration and evaporation, the crude was dissolved in MeOH and p-fluorobenzylamine (3.5 eq.) added. After being refluxed overnight, the residue was washed with Et2O/EP. The solid was dissolved in MeOH and NaCNBH3 (1.4 eq.), AcONa (1.6 eq.), HCHO 37% (1 eq.) were added. The reaction mixture was stirred at room temperature overnight. The product was purified by preparative HPLC (C18, gradient CH3CN/H2O+0.01% TFA) to obtain the title compound (C-40) as trifluoro acetate salt.

Workup

  1. filtrationAfter filtration and evaporation
  2. dissolutionthe crude was dissolved in MeOH
  3. temperatureAfter being refluxed overnight
  4. washthe residue was washed with Et2O/EP
  5. dissolutionThe solid was dissolved in MeOH
  6. customThe product was purified by preparative HPLC (C18, gradient CH3CN/H2O+0.01% TFA)

Sources & evidence

ORD record
ord-3e016da69cc347a8840ee2f91f42a0ee
Source dataset
uspto-grants-2008_12
Patent number
US07459452B2

Reaction notes

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