1,1-Dichloroethane → HCID 68106953, compound

HRID 2403621Notes

Reaction equation

HRID 2403621 reaction equation
[CH:1]([C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]([CH:26]=[CH:27][CH:28]=2)[CH2:12][N:13]([CH3:25])[C:14](=[O:24])[CH2:15][NH:16]C(=O)OC(C)(C)C)=[CH:5][CH:4]=1)=O.[NH:29]1[CH2:33][CH2:32][CH2:31][C@@H:30]1[CH2:34][OH:35].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:50]C(Cl)C>C(O)(=O)C>[ClH:50].[ClH:50].[ClH:50].[OH:35][CH2:34][C@@H:30]1[CH2:31][CH2:32][CH2:33][N:29]1[CH2:1][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]([CH:26]=[CH:27][CH:28]=2)[CH2:12][N:13]([CH3:25])[C:14](=[O:24])[CH2:15][NH2:16])=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 63651,1-DichloroethaneHCID 2724541Prolinol, (R)-HCID 5049666Sodium triacetoxyborohydrideHCID 86667977HCID 86667977, compound

Product 1

HCID 68106953HCID 68106953, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

tert-Butyl (2-{[3-(6-formylpyridin-3-yl)benzyl](methyl)amino}-2-oxoethyl)carbamate (150 mg) and (2R)-pyrrolidin-2-ylmethanol (59 mg) was dissolved in dichloroethane (1 ml) and acetic acid (1 ml), followed by stirring at 60° C. for 30 minutes. Sodium triacetoxyborohydride (166 mg) was added thereto, followed by stirring at 60° C. for 3 hours. The reaction mixture was concentrated under reduced pressure, and to the obtained residue was added a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with CHCl3. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH). The product was dissolved in MeOH (3 ml), and 4 M hydrogen chloride/EtOAc (1 ml) was added thereto, followed by stirring at room temperature overnight and concentrating under reduced pressure. Then, EtOH was added thereto, and then the precipitated solid was collected by filtration to obtain N-[3-(6-{[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl}pyridin-3-yl)benzyl]-N-methylglycinamide trihydrochloride (43 mg).

Workup

  1. stirringby stirring at 60° C. for 3 hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additionto the obtained residue was added a saturated aqueous sodium hydrogen carbonate solution
  4. extractionfollowed by extraction with CHCl3
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)
  8. dissolutionThe product was dissolved in MeOH (3 ml)
  9. addition4 M hydrogen chloride/EtOAc (1 ml) was added
  10. stirringby stirring at room temperature overnight
  11. concentrationconcentrating under reduced pressure
  12. additionThen, EtOH was added
  13. filtrationthe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-20ed0645f5b0490b8ac91483f02d6747
Source dataset
uspto-grants-2014_08
Patent number
US08802679B2

Reaction notes

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